EAOH
MCID: ATX029
MIFTS: 60

Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia (EAOH)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

MalaCards integrated aliases for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

Name: Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia 57 13 39 70
Aoa1 57 25 20 58 72
Ataxia with Oculomotor Apraxia Type 1 12 25 20 15
Ataxia-Oculomotor Apraxia Type 1 20 58 29 6
Eoca-Ha 57 20 72 54
Eaoh 57 20 43 72
Ataxia-Telangiectasia-Like Syndrome 57 20 36
Ataxia-Oculomotor Apraxia 1 57 20 72
Ataxia-Oculomotor Apraxia Syndrome 57 72
Ataxia with Oculomotor Apraxia 43 6
Aoa 57 72
Early-Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia 43
Early-Onset Ataxia with Oculomotor Apraxia and Hypoalbuminemia 20
Ataxia Early-Onset with Oculomotor Apraxia and Hypoalbuminemia 72
Cerebellar Ataxia, Early-Onset, with Hypoalbuminemia; Eoca-Ha 57
Spinocerebellar Ataxia, Recessive, Non-Friedreich Type 1 43
Cerebellar Ataxia, Early-Onset, with Hypoalbuminemia 57
Spinocerebellar Ataxia with Axonal Neuropathy Type 2 43
Early-Onset Cerebellar Ataxia with Hypoalbuminemia 20
Cerebellar Ataxia Early-Onset with Hypoalbuminemia 72
Spinocerebellar Ataxia, Autosomal Recessive 1 70
Adult Onset Ataxia with Oculomotor Apraxia 43
Ataxia-Oculomotor Apraxia Syndrome; Aoa 57
Ataxia - Telangiectasia-Like Disorder 6
Ataxia-Oculomotor Apraxia 1; Aoa1 57
Ataxia-Oculomotor Apraxia 39
Scan2 43
Scar1 43

Characteristics:

Orphanet epidemiological data:

58
ataxia-oculomotor apraxia type 1
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset is usually in childhood or adolescence (2 to 18 years)
adult onset has been reported
oculomotor apraxia is not always present


HPO:

31
ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset adult onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1168 Definition A rare autosomal recessive cerebellar ataxia, characterized by progressive cerebellar ataxia associated with oculomotor apraxia, severe neuropathy, and hypoalbuminemia. Epidemiology Ataxia-oculomotor apraxia type 1 (AOA1) represents 3.6% of all autosomal recessive cerebellar ataxia (ARCA) in Portugal; in Japan, AOA1 seems to be the most frequent cause of ARCA. In a cohort of 227 patients mostly of French origin with progressive cerebellar ataxia selected after exclusion of Friedreich ataxia, the relative frequency of AOA1 was of 5%. Clinical description Cerebellar ataxia is the first manifestation of AOA1 with a mean age of onset of 4.3 years (2-10 years) and is characterized by progressive gait imbalance followed by dysarthria, and limb dysmetria. Later, peripheral axonal motor neuropathy dominates the clinical picture. Oculomotor apraxia (OMA; inability to coordinate eyes ? head movements: when the head turns toward a lateral target; the head reaches the target before the eyes) is present in almost all individuals with AOA1. Chorea is present at onset in 80% of patients and upper limb dystonia (see this term) occurs in about 50% of individuals. Additional features include square wave jerks, saccadic pursuit and gaze-evoked nystagmus, areflexia followed by severe peripheral neuropathy. Variable intellectual disability is observed. Etiology AOA1 results from mutations in APTX gene (9p13.3) encoding aprataxin which plays a role in DNA -single-strand break repair. Most mutations identified so far are localized in exons 5, 6 and 7. Some correlations between genotype and phenotype have been established: for example severe and persistent choreic phenotype is associated with mutations A198V; truncating mutations are associated with earlier onset and deletions with more severe phenotype and intellectual disability. Diagnostic methods Diagnosis of AOA1 is based on the clinical features, the progressive evolution, the absence of extraneurologic findings and family history. Electromyography findings reveal severe axonal sensory-motor neuropathy. Oculographic recordings demonstrate normal latencies, hypometric saccades, decrease mean gain in amplitude and broken saccades into multiple successive saccades. Cerebral magnetic resonance imagery displays cerebellar atrophy. Hypoalbuminemia and hypercholesterolemia are usual (disease duration is positively correlated with cholesterol and negatively correlated with albumin levels). Diagnosis is confirmed by molecular analysis of APTX gene. Differential diagnosis Differential diagnosis includes Friedreich ataxia, ataxia with vitamin E deficiency, AOA2, ataxia-telangiectasia, ataxia-telangiectasia-like disorder, autosomal recessive spastic ataxia of Charlevoix-Saguenay (see these terms). Antenatal diagnosis Carrier testing for at-risk family members and prenatal testing are possible if both disease-causing alleles in a family are known. Genetic counseling Transmission of AOA1 is autosomal recessive. Genetic counseling is recommended as each sib of an affected individual has 25% chance of being affected, 50% chance of being an asymptomatic carrier, and 25% chance of being neither affected nor a carrier. Management and treatment No specific treatment exists for AOA1 and management is mainly supportive. It includes physical therapy for cerebellar ataxia and disabilities resulting from peripheral neuropathy; educational support for reading and writing difficulties, speech therapy for dysarthria and cognitive impairment. Low-cholesterol diet and hypolipemiant treatment are recommended. Routine follow-up with a neurologist or neurogenetician is suggested. Some therapeutic trials are on the way such as the evaluation of efficacy of Coenzyme Q10 in evolution of the disease. Prognosis AOA1 is a progressive neurodegenerative disorder and most patients usually become wheelchair bound from seven to ten years after onset of the disease.

MalaCards based summary : Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia, also known as aoa1, is related to ataxia-oculomotor apraxia 3 and spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, and has symptoms including tremor, muscle weakness and gait ataxia. An important gene associated with Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia is APTX (Aprataxin), and among its related pathways/superpathways are Base excision repair and Nucleotide excision repair. The drugs Ethanol and Coenzyme Q10 have been mentioned in the context of this disorder. Affiliated tissues include eye, breast and prostate, and related phenotypes are ataxia and gait disturbance

Disease Ontology : 12 An autosomal recessive cerebellar ataxia that is characterized by progressive cerebellar ataxia including oculomotor apraxia, severe neuropathy and hypoalbuminemia, has material basis in autosomal recessive inheritance of mutation in the APTX gene.

MedlinePlus Genetics : 43 Ataxia with oculomotor apraxia is a condition characterized by problems with movement that worsen over time. The hallmark of this condition is poor coordination and balance (ataxia), which is often the first symptom. Most affected people also have oculomotor apraxia, which makes it difficult to move their eyes side-to-side. People with oculomotor apraxia have to turn their head to see things in their side (peripheral) vision.There are several types of ataxia with oculomotor apraxia, the most common of which are types 1, 2, and 4. The types are very similar but are caused by mutations in different genes.Type 1 begins around age 4. In addition to ataxia and oculomotor apraxia, affected individuals can have involuntary jerking movements (chorea) or muscle twitches (myoclonus); these movement problems tend to disappear over time. Individuals with this type may also develop muscle wasting in their hands and feet, which further impairs movement. As in all forms of ataxia with oculomotor apraxia, nearly all people with type 1 develop nerve abnormalities (neuropathy). Neuropathy impairs reflexes and leads to limb weakness and an inability to sense vibrations. Many individuals with ataxia with oculomotor apraxia require wheelchair assistance, typically 10 to 15 years after the start of movement problems.People with some types of ataxia with oculomotor apraxia may have characteristic blood abnormalities. Individuals with type 1 tend to have reduced amounts of a protein called albumin, which transports molecules in the blood. The shortage of albumin likely results in elevated levels of cholesterol circulating in the bloodstream. Increased cholesterol levels raise a person's risk of developing heart disease.Ataxia with oculomotor apraxia type 2 usually begins around age 15. As in type 1, affected individuals may have chorea or myoclonus, although these movement problems persist throughout life in type 2. Neuropathy is also common in this type.A key feature of ataxia with oculomotor apraxia type 2 is high amounts of a protein called alpha-fetoprotein (AFP) in the blood. (Raised levels of this protein are normally seen in the bloodstream of pregnant women.) Individuals with type 2 may also have high amounts of a protein called creatine phosphokinase (CPK) in their blood. This protein is normally found primarily in muscle tissue. The effect of abnormally high levels of AFP or CPK in people with ataxia with oculomotor apraxia type 2 is unknown. Although individuals with type 2 usually have normal albumin levels, cholesterol may be elevated.Ataxia with oculomotor apraxia type 4 begins around age 4. In addition to ataxia and oculomotor apraxia, individuals with this type typically develop dystonia, which is involuntary, sustained muscle tensing that causes unusual positioning of body parts. Dystonia can be the first feature of the condition, and it tends to disappear gradually over time. Muscle wasting in the hands and feet and neuropathy are also common in individuals with type 4.In ataxia with oculomotor apraxia type 4, albumin levels can be low, and cholesterol or AFP can be elevated. However, the amounts of these molecules are normal in many affected individuals.Intelligence is usually not affected by ataxia with oculomotor apraxia, but some people with the condition have intellectual disability.

OMIM® : 57 Ataxia-oculomotor apraxia syndrome is an early-onset autosomal recessive cerebellar ataxia with peripheral axonal neuropathy, oculomotor apraxia (defined as the limitation of ocular movements on command), and hypoalbuminemia (Moreira et al., 2001). (208920) (Updated 05-Apr-2021)

KEGG : 36 Ataxia-telangiectasia-like disorder (ATLD) is a very rare autosomal recessive disorder, caused by mutations in Mre11 gene. Mre11 is a member of the Mre11/Rad50/Nbs1 (MRN) protein complex, that acts as a double-strand break sensor and recruits ATM to broken DNA molecules. The clinical features include the progressive cerebellar ataxia, and they are very similar to those of Ataxia-telangiectasia (A-T). In contrast to A-T, ATLD patients don't show telangiectasia and immune deficiency. Recently, genetic heterogeneity of ATLD, caused by mutation in the PCNA gene, has been reported.

UniProtKB/Swiss-Prot : 72 Ataxia-oculomotor apraxia syndrome: An autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.

GeneReviews: NBK1456

Related Diseases for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Diseases related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 158)
# Related Disease Score Top Affiliating Genes
1 ataxia-oculomotor apraxia 3 31.7 TDP1 SETX APTX
2 spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 31.3 TTPA SETX FXN CACNA1A APTX
3 axonal neuropathy 30.7 TDP1 SETX LIG3
4 ocular motor apraxia 30.5 ATM APTX
5 cerebellar degeneration 30.4 MRE11 CACNA1A ATM
6 dystonia 30.3 TTPA SETX CACNA1A ATM APTX
7 kearns-sayre syndrome 30.2 FXN COQ8A CACNA1A APTX
8 ataxia-telangiectasia 30.2 XRCC1 MRE11 ATM APTX
9 friedreich ataxia 30.1 TTPA SETX FXN CACNA1A APTX
10 autosomal recessive disease 29.9 TTPA PNKP FXN ATM
11 ataxia with vitamin 3 deficiency 29.8 TTPA SIL1 SETX FXN APTX
12 choreatic disease 29.8 SETX FXN CACNA1A APTX
13 oculomotor apraxia 29.6 XRCC1 SETX PNKP MRE11 ATM APTX
14 apraxia 29.6 XRCC1 SIL1 SETX PNKP ATM APTX
15 autosomal dominant cerebellar ataxia 29.4 TTPA TDP1 SPTBN2 SETX PNKP FXN
16 autosomal recessive cerebellar ataxia 28.7 TDP1 SPTBN2 SETX FXN COQ8A CACNA1A
17 hereditary ataxia 27.8 TTPA TDP1 SPTBN2 SIL1 SETX PNKP
18 spinocerebellar ataxia type 1 with axonal neuropathy 27.7 XRCC1 TDP1 SETX POLB PNKP NEIL1
19 ataxia-telangiectasia-like disorder 2 11.9
20 joubert syndrome 6 11.3
21 anemia, sideroblastic, and spinocerebellar ataxia 11.3
22 acrocallosal syndrome 11.2
23 joubert syndrome 1 11.2
24 joubert syndrome 10 11.2
25 joubert syndrome 2 11.2
26 joubert syndrome 3 11.2
27 joubert syndrome 4 11.2
28 joubert syndrome 5 11.2
29 joubert syndrome 7 11.2
30 joubert syndrome 9 11.2
31 joubert syndrome 8 11.2
32 nephronophthisis 12 11.2
33 joubert syndrome 13 11.2
34 meckel syndrome, type 10 11.2
35 joubert syndrome 15 11.2
36 spastic ataxia 5, autosomal recessive 11.2
37 joubert syndrome 17 11.2
38 joubert syndrome 18 11.2
39 nephronophthisis 14 11.2
40 joubert syndrome 20 11.2
41 joubert syndrome 21 11.2
42 joubert syndrome 22 11.2
43 joubert syndrome 23 11.2
44 joubert syndrome 24 11.2
45 joubert syndrome 25 11.2
46 joubert syndrome 26 11.2
47 joubert syndrome 27 11.2
48 joubert syndrome 28 11.2
49 meckel syndrome 13 11.2
50 joubert syndrome 30 11.2

Graphical network of the top 20 diseases related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:



Diseases related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Symptoms & Phenotypes for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Human phenotypes related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

58 31 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%) HP:0001288
3 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
4 medial flaring of the eyebrow 58 31 hallmark (90%) Very frequent (99-80%) HP:0010747
5 mental deterioration 31 occasional (7.5%) HP:0001268
6 choreoathetosis 31 very rare (1%) HP:0001266
7 scoliosis 31 HP:0002650
8 dysarthria 31 HP:0001260
9 tremor 31 HP:0001337
10 muscle weakness 31 HP:0001324
11 cognitive impairment 31 HP:0100543
12 progressive external ophthalmoplegia 31 HP:0000590
13 areflexia 31 HP:0001284
14 hypercholesterolemia 31 HP:0003124
15 dystonia 31 HP:0001332
16 pes cavus 31 HP:0001761
17 hyporeflexia 31 HP:0001265
18 abnormality of the nervous system 58 Very frequent (99-80%)
19 hypoalbuminemia 31 HP:0003073
20 gait ataxia 31 HP:0002066
21 cerebellar atrophy 31 HP:0001272
22 oculomotor apraxia 31 HP:0000657
23 dementia 31 HP:0000726
24 distal sensory impairment 31 HP:0002936
25 distal amyotrophy 31 HP:0003693
26 limb ataxia 31 HP:0002070
27 truncal ataxia 31 HP:0002078
28 decreased number of large peripheral myelinated nerve fibers 31 HP:0003387
29 hypometric saccades 31 HP:0000571
30 gaze-evoked nystagmus 31 HP:0000640
31 axonal degeneration 31 HP:0040078
32 peripheral axonal degeneration 31 HP:0000764

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Spine:
scoliosis

Muscle Soft Tissue:
muscle weakness
distal muscular atrophy due to peripheral neuropathy
muscle coenzyme q deficiency

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
axonal sensory and motor peripheral neuropathy, severe
distal sensory loss
nerve biopsy shows axonal degeneration and axonal sprouting
more
Laboratory Abnormalities:
hypoalbuminemia (in 83%)
hypercholesterolemia (in 75%)

Neurologic Central Nervous System:
dysarthria
tremor
dystonia
gait ataxia
cerebellar atrophy
more
Head And Neck Eyes:
progressive external ophthalmoplegia
hypometric saccades
gaze-evoked nystagmus
oculomotor apraxia (in 86% of patients)

Skeletal Feet:
pes cavus

Clinical features from OMIM®:

208920 (Updated 05-Apr-2021)

UMLS symptoms related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:


tremor; muscle weakness; gait ataxia; cerebellar ataxia; ataxia, truncal

GenomeRNAi Phenotypes related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to GeneCards Suite gene sharing:

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.98 COQ8A FXN
2 Decreased viability GR00221-A-3 9.98 ATM COQ8A
3 Decreased viability GR00221-A-4 9.98 ATM
4 Decreased viability GR00249-S 9.98 CACNA1A PNKP TDP1 XRCC1
5 Decreased viability GR00301-A 9.98 FXN
6 Decreased viability GR00342-S-1 9.98 PNKP
7 Decreased viability GR00342-S-2 9.98 PNKP
8 Decreased viability GR00342-S-3 9.98 PNKP
9 Decreased viability GR00381-A-1 9.98 COQ8A
10 Decreased viability GR00386-A-1 9.98 FEN1 NEIL1 SETX TDP1 TTPA
11 Decreased viability GR00402-S-2 9.98 NTHL1 SETX
12 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.91 LIG3 MRE11 SETX TDP1 XRCC1
13 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.91 ATM LIG3 MRE11 SETX TDP1 XRCC1
14 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.91 ATM FEN1 LIG3 MRE11 SETX TDP1

MGI Mouse Phenotypes related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.25 ATM CACNA1A COQ8A FXN LIG3 MRE11
2 cellular MP:0005384 10.24 APEX1 APTX ATM CACNA1A FEN1 FXN
3 homeostasis/metabolism MP:0005376 10.19 APEX1 APTX ATM CACNA1A COQ8A FEN1
4 embryo MP:0005380 9.97 APEX1 ATM FEN1 FXN LIG3 MRE11
5 muscle MP:0005369 9.7 APEX1 CACNA1A COQ8A FXN LIG3 POLB
6 neoplasm MP:0002006 9.5 APEX1 ATM FEN1 MRE11 NEIL1 NTHL1
7 nervous system MP:0003631 9.47 ATM CACNA1A COQ8A FEN1 FXN LIG3

Drugs & Therapeutics for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Drugs for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ethanol Approved Phase 3 64-17-5 702
2
Coenzyme Q10 Approved, Investigational, Nutraceutical Phase 3 303-98-0 5281915
3
Lecithin Experimental Phase 3 8002-43-5
4 Trace Elements Phase 3
5 Nutrients Phase 3
6 Complement System Proteins Phase 3
7 Vitamins Phase 3
8 Micronutrients Phase 3
9 Ubiquinone Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Evolution of Albumin on AOA1 Patients Supplemented With Coenzyme Q10 Completed NCT02333305 Phase 3

Search NIH Clinical Center for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Genetic Tests for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Genetic tests related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

# Genetic test Affiliating Genes
1 Ataxia-Oculomotor Apraxia Type 1 29 APTX

Anatomical Context for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

MalaCards organs/tissues related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

40
Eye, Breast, Prostate

Publications for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Articles related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

(show top 50) (show all 103)
# Title Authors PMID Year
1
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations. 61 57 6 25
12196655 2002
2
Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. 25 57 6
15699391 2005
3
Aprataxin gene mutations in Tunisian families. 25 57 6
15365154 2004
4
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. 6 57 25
11586299 2001
5
The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. 6 25 57
11586300 2001
6
Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. 25 57 6
11294920 2001
7
Recessive ataxia with ocular apraxia: review of 22 Portuguese patients. 6 25 57
11176957 2001
8
Muscle coenzyme Q10 deficiencies in ataxia with oculomotor apraxia 1. 54 57 6
17242337 2007
9
Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients. 57 6
21465257 2011
10
Very late onset in ataxia oculomotor apraxia type I. 57 6
15852392 2005
11
Ataxia with oculomotor apraxia type 1 in Southern Italy: late onset and variable phenotype. 25 57
15596775 2004
12
Aprataxin mutations are a rare cause of early onset ataxia in Germany. 25 6
15164193 2004
13
Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. 25 6
14506070 2003
14
Phenotypic variability of aprataxin gene mutations. 25 6
12629250 2003
15
Homozygosity mapping of Portuguese and Japanese forms of ataxia-oculomotor apraxia to 9p13, and evidence for genetic heterogeneity. 25 57
11170899 2001
16
Hereditary cerebellar ataxia with peripheral neuropathy and mental retardation. 25 57
10686465 2000
17
Hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA): clinical and neuropathological features of a Japanese family. 57 25
9667774 1998
18
Hereditary motor and sensory neuropathy associated with cerebellar atrophy (HMSNCA): a new disease. 25 57
8583217 1995
19
[A hereditary ataxia associated with hypoalbuminemia and hyperlipidemia--a variant form of Friedreich's disease or a new clinical entity?]. 57 25
1297549 1992
20
Disease-associated mutations inactivate AMP-lysine hydrolase activity of Aprataxin. 6 54
15790557 2005
21
First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery. 6
32214227 2020
22
Spectrum and Prevalence of Pathogenic Variants in Ovarian Cancer Susceptibility Genes in a Group of 333 Patients. 6
30441849 2018
23
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer. 6
29922827 2018
24
Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer. 6
29348823 2017
25
Molecular diversity of combined and complex dystonia: insights from diagnostic exome sequencing. 6
28849312 2017
26
Identification of a novel mutation in the APTX gene associated with ataxia-oculomotor apraxia. 6
28652255 2017
27
Genomic analysis of inherited breast cancer among Palestinian women: Genetic heterogeneity and a founder mutation in TP53. 6
28486781 2017
28
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. 6
28125075 2017
29
Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels. 6
28152038 2017
30
Improving performance of multigene panels for genomic analysis of cancer predisposition. 6
26845104 2016
31
Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. 6
27433846 2016
32
Clinical application of whole-exome sequencing across clinical indications. 6
26633542 2016
33
Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer. 6
27329137 2016
34
Panel Testing for Familial Breast Cancer: Calibrating the Tension Between Research and Clinical Care. 6
26786923 2016
35
Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway. 57
25976310 2015
36
Ataxia telangiectasia: more variation at clinical and cellular levels. 6
25040471 2015
37
Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. 6
25452441 2015
38
Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. 6
24549055 2014
39
Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. 6
24763289 2014
40
Disease-associated MRE11 mutants impact ATM/ATR DNA damage signaling by distinct mechanisms. 6
23912341 2013
41
Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model. 6
24030952 2013
42
Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair. 6
23080121 2012
43
Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. 6
22863007 2012
44
Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling. 6
22705791 2012
45
Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. 6
22006311 2011
46
Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly. 6
21227757 2011
47
Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management. 57
19440741 2010
48
Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage. 57
19643912 2009
49
Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene. 6
19383352 2008
50
DNA single-strand break repair is impaired in aprataxin-related ataxia. 25 61
17315206 2007

Variations for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

ClinVar genetic disease variations for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

6 (show top 50) (show all 436)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 APTX NM_001195248.2(APTX):c.841del (p.Ser281fs) Deletion Pathogenic 4427 rs587776594 GRCh37: 9:32974489-32974489
GRCh38: 9:32974491-32974491
2 APTX NC_000009.12:g.(?_32973498)_(33001604_?)del Deletion Pathogenic 4432 GRCh37:
GRCh38: 9:32973498-33001604
3 APTX NM_001195248.2(APTX):c.484-1G>T SNV Pathogenic 634641 rs1563963464 GRCh37: 9:32986029-32986029
GRCh38: 9:32986031-32986031
4 APTX NM_001195248.2(APTX):c.776del (p.Val259fs) Deletion Pathogenic 635168 rs1563945076 GRCh37: 9:32974554-32974554
GRCh38: 9:32974556-32974556
5 APTX NM_001195248.2(APTX):c.875-1G>A SNV Pathogenic 4430 rs1587330671 GRCh37: 9:32973651-32973651
GRCh38: 9:32973653-32973653
6 APTX NM_001195248.2(APTX):c.689dup (p.Glu232fs) Duplication Pathogenic 4425 rs587776593 GRCh37: 9:32984709-32984710
GRCh38: 9:32984711-32984712
7 APTX NM_001195248.2(APTX):c.617C>T (p.Pro206Leu) SNV Pathogenic 4426 rs121908131 GRCh37: 9:32984782-32984782
GRCh38: 9:32984784-32984784
8 APTX NM_001195248.2(APTX):c.788T>G (p.Val263Gly) SNV Pathogenic 4428 rs121908132 GRCh37: 9:32974542-32974542
GRCh38: 9:32974544-32974544
9 APTX NM_001195248.2(APTX):c.602A>G (p.His201Arg) SNV Pathogenic 4429 rs121908133 GRCh37: 9:32984797-32984797
GRCh38: 9:32984799-32984799
10 APTX NM_001195248.2(APTX):c.697A>T (p.Lys233Ter) SNV Pathogenic 426093 rs1114167423 GRCh37: 9:32984702-32984702
GRCh38: 9:32984704-32984704
11 APTX NM_001195248.2(APTX):c.875-2A>G SNV Pathogenic 434253 rs904293109 GRCh37: 9:32973652-32973652
GRCh38: 9:32973654-32973654
12 MRE11 NM_005591.3(MRE11):c.664A>T (p.Lys222Ter) SNV Pathogenic 659921 rs371455048 GRCh37: 11:94204921-94204921
GRCh38: 11:94471755-94471755
13 MRE11 NM_005590.4(MRE11):c.1047_1048del (p.Glu350fs) Deletion Pathogenic 660377 rs1591688367 GRCh37: 11:94201029-94201030
GRCh38: 11:94467863-94467864
14 MRE11 NM_005591.3(MRE11):c.1447C>T (p.Arg483Ter) SNV Pathogenic 231449 rs780001540 GRCh37: 11:94192627-94192627
GRCh38: 11:94459461-94459461
15 MRE11 NC_000011.10:g.(?_94470461)_(94492811_?)del Deletion Pathogenic 833144 GRCh37: 11:94203627-94225977
GRCh38:
16 MRE11 NM_005591.4(MRE11):c.571C>T (p.Arg191Ter) SNV Pathogenic 825924 rs1157413766 GRCh37: 11:94209543-94209543
GRCh38: 11:94476377-94476377
17 MRE11 NM_005591.3(MRE11):c.1414G>T (p.Glu472Ter) SNV Pathogenic 481748 rs1376550081 GRCh37: 11:94192660-94192660
GRCh38: 11:94459494-94459494
18 MRE11 NM_005591.3(MRE11):c.504_511del (p.Leu169fs) Deletion Pathogenic 185530 rs786202253 GRCh37: 11:94211934-94211941
GRCh38: 11:94478768-94478775
19 MRE11 NM_005591.3(MRE11):c.1143del (p.Phe381fs) Deletion Pathogenic 216094 rs863224508 GRCh37: 11:94197361-94197361
GRCh38: 11:94464195-94464195
20 MRE11 NM_005591.4(MRE11):c.552del (p.Pro185fs) Deletion Pathogenic 941113 GRCh37: 11:94209562-94209562
GRCh38: 11:94476396-94476396
21 MRE11 NM_005591.4(MRE11):c.1603G>T (p.Glu535Ter) SNV Pathogenic 946577 GRCh37: 11:94180565-94180565
GRCh38: 11:94447399-94447399
22 MRE11 NM_005591.4(MRE11):c.1326+1del Deletion Pathogenic 967050 GRCh37: 11:94194101-94194101
GRCh38: 11:94460935-94460935
23 MRE11 NM_005591.3(MRE11):c.659+1G>A SNV Pathogenic 230014 rs759130031 GRCh37: 11:94209454-94209454
GRCh38: 11:94476288-94476288
24 MRE11 NM_005590.4(MRE11):c.1726C>T (p.Arg576Ter) SNV Pathogenic 184445 rs774277300 GRCh37: 11:94180442-94180442
GRCh38: 11:94447276-94447276
25 MRE11 NM_005591.4(MRE11):c.1897C>T (p.Arg633Ter) SNV Pathogenic 8782 rs137852759 GRCh37: 11:94170372-94170372
GRCh38: 11:94437206-94437206
26 MRE11 NM_005591.4(MRE11):c.818_819CT[1] (p.Leu274fs) Microsatellite Pathogenic 807630 rs1565228898 GRCh37: 11:94204764-94204765
GRCh38: 11:94471598-94471599
27 MRE11 NM_005591.4(MRE11):c.1112dup (p.Gly372fs) Duplication Pathogenic 807446 rs1591681273 GRCh37: 11:94197391-94197392
GRCh38: 11:94464225-94464226
28 MRE11 NM_005591.4(MRE11):c.1714C>T (p.Arg572Ter) SNV Pathogenic 8784 rs137852761 GRCh37: 11:94180454-94180454
GRCh38: 11:94447288-94447288
29 APTX NM_001195248.2(APTX):c.668T>C (p.Leu223Pro) SNV Pathogenic 4433 rs267606665 GRCh37: 9:32984731-32984731
GRCh38: 9:32984733-32984733
30 APTX NM_001195248.2(APTX):c.336_337del (p.His112fs) Microsatellite Pathogenic 1034384 GRCh37: 9:32987688-32987689
GRCh38: 9:32987690-32987691
31 APTX NM_001195248.2(APTX):c.484-2A>T SNV Pathogenic 1034385 GRCh37: 9:32986030-32986030
GRCh38: 9:32986032-32986032
32 APTX NM_001195248.2(APTX):c.505C>T (p.Gln169Ter) SNV Pathogenic 1034386 GRCh37: 9:32986007-32986007
GRCh38: 9:32986009-32986009
33 MRE11 NM_005591.3(MRE11):c.1090C>T (p.Arg364Ter) SNV Pathogenic 140953 rs371077728 GRCh37: 11:94200987-94200987
GRCh38: 11:94467821-94467821
34 MRE11 NM_005590.4(MRE11):c.1516G>T (p.Glu506Ter) SNV Pathogenic 140941 rs587781384 GRCh37: 11:94189489-94189489
GRCh38: 11:94456323-94456323
35 MRE11 NM_005590.4(MRE11):c.1222dup (p.Thr408fs) Duplication Pathogenic 184556 rs774440500 GRCh37: 11:94197281-94197282
GRCh38: 11:94464115-94464116
36 APTX NM_001195248.2(APTX):c.837G>A (p.Trp279Ter) SNV Pathogenic 4431 rs104894103 GRCh37: 9:32974493-32974493
GRCh38: 9:32974495-32974495
37 MRE11 NM_005591.3(MRE11):c.77T>C (p.Met26Thr) SNV Likely pathogenic 182553 rs372068015 GRCh37: 11:94224075-94224075
GRCh38: 11:94490909-94490909
38 MRE11 NM_005591.4(MRE11):c.350A>G (p.Asn117Ser) SNV Likely pathogenic 8783 rs137852760 GRCh37: 11:94212892-94212892
GRCh38: 11:94479726-94479726
39 MRE11 NM_005591.3(MRE11):c.21-6_26del Deletion Likely pathogenic 127979 rs587780138 GRCh37: 11:94224126-94224137
GRCh38: 11:94490960-94490971
40 MRE11 NM_005591.3(MRE11):c.402+2_402+3delinsGGG Indel Likely pathogenic 481774 rs1555015413 GRCh37: 11:94212837-94212838
GRCh38: 11:94479671-94479672
41 APTX NM_001195248.2(APTX):c.124C>T (p.Arg42Ter) SNV Likely pathogenic 420789 rs201912053 GRCh37: 9:32989766-32989766
GRCh38: 9:32989768-32989768
42 PNKP NM_007254.4(PNKP):c.1295_1298+6del Deletion Likely pathogenic 159788 rs587784366 GRCh37: 19:50365023-50365032
GRCh38: 19:49861766-49861775
43 MRE11 NM_005591.4(MRE11):c.1225+2T>A SNV Likely pathogenic 937370 GRCh37: 11:94197277-94197277
GRCh38: 11:94464111-94464111
44 MRE11 and overlap with 1 gene(s) NC_000011.9:g.(?_94194092)_(94212937_?)dup Duplication Likely pathogenic 658977 GRCh37: 11:94194092-94212937
GRCh38: 11:94460926-94479771
45 APTX NM_001195248.2(APTX):c.46C>T (p.Arg16Ter) SNV Likely pathogenic 930027 GRCh37: 9:32989844-32989844
GRCh38: 9:32989846-32989846
46 SETX NM_015046.7(SETX):c.1856_1863del (p.Ser618_Tyr619insTer) Deletion Likely pathogenic 977926 GRCh37: 9:135205122-135205129
GRCh38: 9:132329735-132329742
47 MRE11 NM_005591.3(MRE11):c.1327-2A>G SNV Likely pathogenic 240184 rs878854776 GRCh37: 11:94192749-94192749
GRCh38: 11:94459583-94459583
48 MRE11 NM_005591.3(MRE11):c.1724G>A (p.Gly575Asp) SNV Uncertain significance 220769 rs376555330 GRCh37: 11:94180444-94180444
GRCh38: 11:94447278-94447278
49 MRE11 NM_005591.3(MRE11):c.314A>C (p.Lys105Thr) SNV Uncertain significance 407891 rs1025272236 GRCh37: 11:94219090-94219090
GRCh38: 11:94485924-94485924
50 SETX NM_015046.7(SETX):c.12_14TTG[1] (p.Cys5del) Microsatellite Uncertain significance 448306 rs774123592 GRCh37: 9:135224799-135224801
GRCh38: 9:132349412-132349414

UniProtKB/Swiss-Prot genetic disease variations for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia:

72
# Symbol AA change Variation ID SNP ID
1 APTX p.Lys211Gln VAR_018794
2 APTX p.Ala212Val VAR_018795 rs748165574
3 APTX p.Arg213His VAR_018796 rs150886026
4 APTX p.His215Arg VAR_018797 rs121908133
5 APTX p.Pro220Leu VAR_018798 rs121908131
6 APTX p.Val277Gly VAR_018799 rs121908132
7 APTX p.Asp281Gly VAR_018800
8 APTX p.Trp293Arg VAR_018801 rs773393618
9 APTX p.Leu237Pro VAR_025365 rs267606665

Expression for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Search GEO for disease gene expression data for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia.

Pathways for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Pathways related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to KEGG:

36
# Name Kegg Source Accession
1 Base excision repair hsa03410
2 Nucleotide excision repair hsa03420
3 Homologous recombination hsa03440

Pathways related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.7 XRCC1 TDP1 POLB PNKP NTHL1 NEIL1
2
Show member pathways
12.6 XRCC1 POLB PNKP NTHL1 NEIL1 LIG3
3
Show member pathways
12.58 POLB NTHL1 MRE11 CACNA1A ATM
4 12.23 XRCC1 TDP1 PNKP MRE11 FEN1 ATM
5
Show member pathways
11.88 XRCC1 POLB PNKP NTHL1 MRE11 LIG3
6 10.88 PNKP MRE11 FEN1
7
Show member pathways
10.81 NTHL1 NEIL1
8
Show member pathways
10.57 MRE11 ATM

GO Terms for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

Cellular components related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.18 TTPA TDP1 SPTBN2 SETX POLB NEIL1
2 nucleus GO:0005634 10 XRCC1 TDP1 SETX POLB PNKP NTHL1
3 mitochondrion GO:0005739 9.87 PNKP NTHL1 LIG3 FXN FEN1 COQ8A
4 nucleolus GO:0005730 9.8 XRCC1 SETX PNKP FEN1 ATM APTX
5 nucleoplasm GO:0005654 9.77 XRCC1 TDP1 SETX POLB PNKP NTHL1
6 chromosome, telomeric region GO:0000781 9.1 XRCC1 SETX MRE11 FEN1 ATM APEX1

Biological processes related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to GeneCards Suite gene sharing:

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 DNA replication GO:0006260 9.85 POLB MRE11 LIG3 FEN1 ATM
2 DNA recombination GO:0006310 9.81 SETX MRE11 LIG3 APEX1
3 double-strand break repair via homologous recombination GO:0000724 9.8 XRCC1 MRE11 LIG3 FEN1 ATM
4 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.8 TDP1 PNKP MRE11 FEN1 APTX APEX1
5 double-strand break repair via nonhomologous end joining GO:0006303 9.78 XRCC1 POLB MRE11 ATM
6 cellular response to DNA damage stimulus GO:0006974 9.77 XRCC1 TDP1 SETX POLB PNKP NTHL1
7 cellular response to hydrogen peroxide GO:0070301 9.75 SETX FXN APEX1
8 double-strand break repair GO:0006302 9.73 TDP1 SETX MRE11 LIG3 FEN1 APTX
9 telomere maintenance GO:0000723 9.72 MRE11 ATM APEX1
10 nucleotide-excision repair, DNA gap filling GO:0006297 9.67 XRCC1 POLB LIG3
11 base-excision repair GO:0006284 9.63 XRCC1 POLB NTHL1 NEIL1 FEN1 APEX1
12 single strand break repair GO:0000012 9.61 XRCC1 TDP1 APTX
13 DNA-dependent DNA replication GO:0006261 9.6 POLB PNKP
14 DNA double-strand break processing GO:0000729 9.59 MRE11 ATM
15 V(D)J recombination GO:0033151 9.58 LIG3 ATM
16 depyrimidination GO:0045008 9.57 NTHL1 NEIL1
17 DNA ligation GO:0006266 9.56 LIG3 APTX
18 negative regulation of protein ADP-ribosylation GO:0010836 9.54 XRCC1 PNKP
19 base-excision repair, DNA ligation GO:0006288 9.54 XRCC1 POLB LIG3
20 base-excision repair, base-free sugar-phosphate removal GO:0006286 9.52 POLB APEX1
21 DNA repair GO:0006281 9.44 XRCC1 TDP1 SETX POLB PNKP NTHL1

Molecular functions related to Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.51 XRCC1 TTPA TDP1 SPTBN2 SIL1 SETX
2 hydrolase activity GO:0016787 10.09 TDP1 SETX PNKP NTHL1 NEIL1 MRE11
3 DNA binding GO:0003677 10.07 SETX POLB NTHL1 NEIL1 MRE11 LIG3
4 catalytic activity GO:0003824 9.92 PNKP NTHL1 NEIL1 FEN1 APTX
5 nuclease activity GO:0004518 9.76 TDP1 MRE11 FEN1 APEX1
6 endonuclease activity GO:0004519 9.65 PNKP NTHL1 MRE11 FEN1 APEX1
7 double-stranded DNA binding GO:0003690 9.63 TDP1 PNKP NTHL1 MRE11 FEN1 APTX
8 exonuclease activity GO:0004527 9.62 TDP1 MRE11 FEN1 APEX1
9 3'-5' exonuclease activity GO:0008408 9.57 MRE11 APEX1
10 5'-3' exonuclease activity GO:0008409 9.55 MRE11 FEN1
11 RNA-DNA hybrid ribonuclease activity GO:0004523 9.54 FEN1 APEX1
12 DNA N-glycosylase activity GO:0019104 9.51 NTHL1 NEIL1
13 endodeoxyribonuclease activity GO:0004520 9.49 MRE11 APEX1
14 class I DNA-(apurinic or apyrimidinic site) endonuclease activity GO:0140078 9.48 NTHL1 NEIL1
15 double-stranded DNA exodeoxyribonuclease activity GO:0008309 9.4 FEN1 APEX1
16 DNA-(apurinic or apyrimidinic site) endonuclease activity GO:0003906 9.26 POLB NTHL1 NEIL1 APEX1
17 damaged DNA binding GO:0003684 9.17 XRCC1 POLB PNKP NEIL1 FEN1 APTX

Sources for Ataxia, Early-Onset, with Oculomotor Apraxia and Hypoalbuminemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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