AOA4
MCID: ATX033
MIFTS: 27

Ataxia-Oculomotor Apraxia 4 (AOA4)

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

Aliases & Classifications for Ataxia-Oculomotor Apraxia 4

MalaCards integrated aliases for Ataxia-Oculomotor Apraxia 4:

Name: Ataxia-Oculomotor Apraxia 4 58 76 30 6
Aoa4 58 54 60 76
Ataxia-Oculomotor Apraxia Type 4 54 60 17
Ataxia with Oculomotor Apraxia Type 4 54
Ataxia-Oculomotor Apraxia, Type 4 41
Ataxia-Oculomotor Apraxia-4 54

Characteristics:

Orphanet epidemiological data:

60
ataxia-oculomotor apraxia type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
rapidly progressive
onset in first decade (range 1 to 9 years)
most patients become wheelchair-bound in the second or third decades
high prevalence among individuals of portuguese descent


HPO:

33
ataxia-oculomotor apraxia 4:
Onset and clinical course rapidly progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Ataxia-Oculomotor Apraxia 4

OMIM : 58 Ataxia-oculomotor apraxia-4 is an autosomal recessive neurologic disorder characterized by onset of dystonia and ataxia in the first decade. Additional features include oculomotor apraxia and peripheral neuropathy. Some patients may show cognitive impairment. The disorder is progressive, and most patients become wheelchair-bound in the second or third decade (summary by Bras et al., 2015). For a discussion of genetic heterogeneity of ataxia-oculomotor apraxia, see AOA1 (208920). (616267)

MalaCards based summary : Ataxia-Oculomotor Apraxia 4, also known as aoa4, is related to ataxia and polyneuropathy, adult-onset and apraxia. An important gene associated with Ataxia-Oculomotor Apraxia 4 is PNKP (Polynucleotide Kinase 3'-Phosphatase). Affiliated tissues include eye, and related phenotypes are cognitive impairment and ataxia

UniProtKB/Swiss-Prot : 76 Ataxia-oculomotor apraxia 4: An autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy.

Related Diseases for Ataxia-Oculomotor Apraxia 4

Diseases in the Ataxia-Oculomotor Apraxia 4 family:

Ataxia-Oculomotor Apraxia 3

Diseases related to Ataxia-Oculomotor Apraxia 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 ataxia and polyneuropathy, adult-onset 10.2
2 apraxia 10.2
3 astrocytoma 10.2
4 pilocytic astrocytoma 10.2
5 microcephaly, seizures, and developmental delay 10.2

Graphical network of the top 20 diseases related to Ataxia-Oculomotor Apraxia 4:



Diseases related to Ataxia-Oculomotor Apraxia 4

Symptoms & Phenotypes for Ataxia-Oculomotor Apraxia 4

Human phenotypes related to Ataxia-Oculomotor Apraxia 4:

60 33 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cognitive impairment 60 33 occasional (7.5%) Frequent (79-30%) HP:0100543
2 ataxia 60 33 Obligate (100%) HP:0001251
3 peripheral neuropathy 60 33 Frequent (79-30%) HP:0009830
4 dystonia 60 33 Frequent (79-30%) HP:0001332
5 oculomotor apraxia 60 33 Frequent (79-30%) HP:0000657
6 obesity 60 Frequent (79-30%)
7 dysarthria 60 Occasional (29-5%)
8 tetraplegia 33 HP:0002445
9 abnormality of saccadic eye movements 60 Occasional (29-5%)
10 pes cavus 60 Occasional (29-5%)
11 kyphoscoliosis 60 Occasional (29-5%)
12 areflexia 33 HP:0001284
13 dyslexia 60 Occasional (29-5%)
14 cerebellar atrophy 33 HP:0001272
15 distal lower limb muscle weakness 60 Occasional (29-5%)
16 muscular dystrophy 60 Occasional (29-5%)
17 sensorimotor neuropathy 60 Occasional (29-5%)
18 sensory impairment 60 Occasional (29-5%)
19 postural instability 60 Occasional (29-5%)
20 telangiectasia 60 Excluded (0%)
21 dyscalculia 60 Occasional (29-5%)
22 progressive distal muscular atrophy 60 Occasional (29-5%)
23 short attention span 60 Occasional (29-5%)
24 abnormality of toe 60 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
ataxia
tetraplegia
dystonia
cerebellar atrophy
cognitive impairment (in some patients)

Head And Neck Eyes:
oculomotor apraxia

Laboratory Abnormalities:
increased alpha-fetoprotein (in some patients)
increased cholesterol (in some patients)

Neurologic Peripheral Nervous System:
peripheral neuropathy
areflexia
impaired vibration sense

Muscle Soft Tissue:
distal muscle weakness and atrophy

Clinical features from OMIM:

616267

Drugs & Therapeutics for Ataxia-Oculomotor Apraxia 4

Search Clinical Trials , NIH Clinical Center for Ataxia-Oculomotor Apraxia 4

Genetic Tests for Ataxia-Oculomotor Apraxia 4

Genetic tests related to Ataxia-Oculomotor Apraxia 4:

# Genetic test Affiliating Genes
1 Ataxia-Oculomotor Apraxia 4 30 PNKP

Anatomical Context for Ataxia-Oculomotor Apraxia 4

MalaCards organs/tissues related to Ataxia-Oculomotor Apraxia 4:

42
Eye

Publications for Ataxia-Oculomotor Apraxia 4

Articles related to Ataxia-Oculomotor Apraxia 4:

# Title Authors Year
1
Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma. ( 29498415 )
2018
2
Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4. ( 25728773 )
2015
3
Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations. ( 23224214 )
2013
4
Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. ( 20118933 )
2010

Variations for Ataxia-Oculomotor Apraxia 4

UniProtKB/Swiss-Prot genetic disease variations for Ataxia-Oculomotor Apraxia 4:

76
# Symbol AA change Variation ID SNP ID
1 PNKP p.Gly375Trp VAR_073369 rs786203983

ClinVar genetic disease variations for Ataxia-Oculomotor Apraxia 4:

6 (show all 30)
# Gene Variation Type Significance SNP ID Assembly Location
1 PNKP NM_007254.4(PNKP): c.1253_1269dup (p.Thr424Glyfs) duplication Pathogenic rs587784365 GRCh38 Chromosome 19, 49861801: 49861817
2 PNKP NM_007254.4(PNKP): c.1253_1269dup (p.Thr424Glyfs) duplication Pathogenic rs587784365 GRCh37 Chromosome 19, 50365058: 50365074
3 PNKP NM_007254.3(PNKP): c.901C> T (p.Arg301Trp) single nucleotide variant Uncertain significance rs201503405 GRCh37 Chromosome 19, 50365830: 50365830
4 PNKP NM_007254.3(PNKP): c.901C> T (p.Arg301Trp) single nucleotide variant Uncertain significance rs201503405 GRCh38 Chromosome 19, 49862573: 49862573
5 PNKP NM_007254.3(PNKP): c.416G> A (p.Arg139His) single nucleotide variant Conflicting interpretations of pathogenicity rs34472250 GRCh37 Chromosome 19, 50368466: 50368466
6 PNKP NM_007254.3(PNKP): c.416G> A (p.Arg139His) single nucleotide variant Conflicting interpretations of pathogenicity rs34472250 GRCh38 Chromosome 19, 49865209: 49865209
7 PNKP NM_007254.3(PNKP): c.1123G> T (p.Gly375Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs786203983 GRCh38 Chromosome 19, 49862188: 49862188
8 PNKP NM_007254.3(PNKP): c.1123G> T (p.Gly375Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs786203983 GRCh37 Chromosome 19, 50365445: 50365445
9 PNKP NM_007254.3(PNKP): c.1322_1323insAGCCG (p.Gly442Alafs) insertion Pathogenic rs886037744 GRCh38 Chromosome 19, 49861671: 49861672
10 PNKP NM_007254.3(PNKP): c.1322_1323insAGCCG (p.Gly442Alafs) insertion Pathogenic rs886037744 GRCh37 Chromosome 19, 50364928: 50364929
11 PNKP NM_007254.3(PNKP): c.1549_1550insTGTACTGC (p.Gln517Leufs) insertion Pathogenic rs1555810613 GRCh37 Chromosome 19, 50364521: 50364522
12 PNKP NM_007254.3(PNKP): c.1549_1550insTGTACTGC (p.Gln517Leufs) insertion Pathogenic rs1555810613 GRCh38 Chromosome 19, 49861264: 49861265
13 PNKP NM_007254.3(PNKP): c.1221_1223delCAC (p.Thr408del) deletion Likely pathogenic rs786205207 GRCh38 Chromosome 19, 49861847: 49861849
14 PNKP NM_007254.3(PNKP): c.1221_1223delCAC (p.Thr408del) deletion Likely pathogenic rs786205207 GRCh37 Chromosome 19, 50365104: 50365106
15 PNKP NM_007254.2(PNKP): c.1003G> T (p.Gly335Cys) single nucleotide variant Uncertain significance rs768567927 GRCh37 Chromosome 19, 50365654: 50365654
16 PNKP NM_007254.2(PNKP): c.1003G> T (p.Gly335Cys) single nucleotide variant Uncertain significance rs768567927 GRCh38 Chromosome 19, 49862397: 49862397
17 PNKP NM_007254.3(PNKP): c.1559A> G (p.Glu520Gly) single nucleotide variant Uncertain significance rs886043128 GRCh37 Chromosome 19, 50364512: 50364512
18 PNKP NM_007254.3(PNKP): c.1559A> G (p.Glu520Gly) single nucleotide variant Uncertain significance rs886043128 GRCh38 Chromosome 19, 49861255: 49861255
19 PNKP NM_007254.3(PNKP): c.1381A> G (p.Asn461Asp) single nucleotide variant Uncertain significance rs775762473 GRCh37 Chromosome 19, 50364870: 50364870
20 PNKP NM_007254.3(PNKP): c.1381A> G (p.Asn461Asp) single nucleotide variant Uncertain significance rs775762473 GRCh38 Chromosome 19, 49861613: 49861613
21 PNKP NM_007254.3(PNKP): c.1389T> G (p.Phe463Leu) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 49861508: 49861508
22 PNKP NM_007254.3(PNKP): c.1389T> G (p.Phe463Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 50364765: 50364765
23 PNKP NM_007254.3(PNKP): c.1430T> C (p.Met477Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 50364724: 50364724
24 PNKP NM_007254.3(PNKP): c.1430T> C (p.Met477Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 49861467: 49861467
25 PNKP NM_007254.3(PNKP): c.1003G> A (p.Gly335Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 49862397: 49862397
26 PNKP NM_007254.3(PNKP): c.1003G> A (p.Gly335Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 50365654: 50365654
27 PNKP NM_007254.3(PNKP): c.131G> A (p.Arg44Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 49867074: 49867074
28 PNKP NM_007254.3(PNKP): c.131G> A (p.Arg44Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 50370331: 50370331
29 PNKP NM_007254.3(PNKP): c.1052C> T (p.Pro351Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 50365516: 50365516
30 PNKP NM_007254.3(PNKP): c.1052C> T (p.Pro351Leu) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 49862259: 49862259

Expression for Ataxia-Oculomotor Apraxia 4

Search GEO for disease gene expression data for Ataxia-Oculomotor Apraxia 4.

Pathways for Ataxia-Oculomotor Apraxia 4

GO Terms for Ataxia-Oculomotor Apraxia 4

Sources for Ataxia-Oculomotor Apraxia 4

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