AOA4
MCID: ATX033
MIFTS: 33

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 57 72 29 6
Aoa4 57 20 58 72
Ataxia-Oculomotor Apraxia Type 4 20 58 17
Ataxia with Oculomotor Apraxia Type 4 20
Ataxia-Oculomotor Apraxia, Type 4 39
Ataxia-Oculomotor Apraxia-4 20

Characteristics:

Orphanet epidemiological data:

58
ataxia-oculomotor apraxia type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM®:

57 (Updated 20-May-2021)
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

Inheritance:
autosomal recessive


HPO:

31
ataxia-oculomotor apraxia 4:
Inheritance autosomal recessive inheritance
Onset and clinical course rapidly progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases


Summaries for Ataxia-Oculomotor Apraxia 4

OMIM® : 57 Ataxia-oculomotor apraxia-4 (AOA4) 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) (Updated 20-May-2021)

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

UniProtKB/Swiss-Prot : 72 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

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:

58 31 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 obligate (100%) Obligate (100%) HP:0001251
2 cognitive impairment 58 31 occasional (7.5%) Frequent (79-30%) HP:0100543
3 obesity 58 31 frequent (33%) Frequent (79-30%) HP:0001513
4 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
5 oculomotor apraxia 58 31 frequent (33%) Frequent (79-30%) HP:0000657
6 dysarthria 58 31 occasional (7.5%) Occasional (29-5%) HP:0001260
7 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
8 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
9 dyslexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0010522
10 distal lower limb muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0009053
11 muscular dystrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003560
12 sensory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0003474
13 short attention span 58 31 occasional (7.5%) Occasional (29-5%) HP:0000736
14 postural instability 58 31 occasional (7.5%) Occasional (29-5%) HP:0002172
15 sensorimotor neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0007141
16 dyscalculia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002442
17 abnormal saccadic eye movements 58 31 occasional (7.5%) Occasional (29-5%) HP:0000570
18 abnormality of toe 58 31 occasional (7.5%) Occasional (29-5%) HP:0001780
19 progressive distal muscular atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008955
20 peripheral neuropathy 58 31 Frequent (79-30%) HP:0009830
21 tetraplegia 31 HP:0002445
22 areflexia 31 HP:0001284
23 cerebellar atrophy 31 HP:0001272
24 telangiectasia 58 Excluded (0%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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:
areflexia
peripheral neuropathy
impaired vibration sense

Muscle Soft Tissue:
distal muscle weakness and atrophy

Clinical features from OMIM®:

616267 (Updated 20-May-2021)

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 29 PNKP

Anatomical Context for Ataxia-Oculomotor Apraxia 4

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

40
Eye, Cerebellum

Publications for Ataxia-Oculomotor Apraxia 4

Articles related to Ataxia-Oculomotor Apraxia 4:

(show all 21)
# Title Authors PMID Year
1
Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4. 57 6
25728773 2015
2
The polynucleotide kinase 3'-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25. 6 61
30039206 2018
3
Mutation in PNKP presenting initially as axonal Charcot-Marie-Tooth disease. 6
27066567 2015
4
Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations. 6
23224214 2013
5
Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. 6
20118933 2010
6
Autosomal Recessive Cerebellar Ataxias With Elevated Alpha-Fetoprotein: Uncommon Diseases, Common Biomarker. 61
33044027 2020
7
Comparative study of preimplantation development following distinct assisted oocyte activation protocols in a PLC-zeta knockout mouse model. 61
32898251 2020
8
Pathological mutations in PNKP trigger defects in DNA single-strand break repair but not DNA double-strand break repair. 61
32504494 2020
9
Linker region is required for efficient nuclear localization of polynucleotide kinase phosphatase. 61
32970693 2020
10
From congenital microcephaly to adult onset cerebellar ataxia: Distinct and overlapping phenotypes in patients with PNKP gene mutations. 61
31436889 2019
11
Compound Heterozygous Mutations in PNKP Gene in an Iranian Child with Microcephaly, Seizures, and Developmental Delay. 61
31707899 2019
12
Ataxia with Oculomotor Apraxia Type 4 with PNKP Common "Portuguese" and Novel Mutations in Two Belarusian Families. 61
31061747 2019
13
Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature. 61
31656689 2019
14
A Novel Homozygous Variant in the Fork-Head-Associated Domain of Polynucleotide Kinase Phosphatase in a Patient Affected by Late-Onset Ataxia With Oculomotor Apraxia Type 4. 61
32010037 2019
15
Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma. 61
29498415 2018
16
[Ataxia with oculomotor apraxia type 4 detected by next-generation sequencing]. 61
29652299 2018
17
The Rev1 interacting region (RIR) motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair. 61
28821613 2017
18
Neurological disorders associated with DNA strand-break processing enzymes. 61
27470939 2017
19
Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease. 61
27125728 2017
20
Expanding the ataxia with oculomotor apraxia type 4 phenotype. 61
27066586 2016
21
Ataxia with Oculomotor Apraxia Type 2 61
20301333 2004

Variations for Ataxia-Oculomotor Apraxia 4

ClinVar genetic disease variations for Ataxia-Oculomotor Apraxia 4:

6 (show all 24)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PNKP NM_007254.4(PNKP):c.148C>G (p.Gln50Glu) SNV Pathogenic 692103 rs756746191 GRCh37: 19:50370314-50370314
GRCh38: 19:49867057-49867057
2 PNKP NM_007254.4(PNKP):c.1322_1323insAGCCG (p.Gly442fs) Insertion Pathogenic 187767 rs886037744 GRCh37: 19:50364928-50364929
GRCh38: 19:49861671-49861672
3 PNKP NM_007254.4(PNKP):c.1549_1550insTGTACTGC (p.Gln517fs) Insertion Pathogenic 187768 rs1555810613 GRCh37: 19:50364521-50364522
GRCh38: 19:49861264-49861265
4 PNKP NM_007254.4(PNKP):c.1123G>T (p.Gly375Trp) SNV Pathogenic 187766 rs786203983 GRCh37: 19:50365445-50365445
GRCh38: 19:49862188-49862188
5 PNKP NM_007254.4(PNKP):c.85del (p.Gln29fs) Deletion Pathogenic 1033200 GRCh37: 19:50370377-50370377
GRCh38: 19:49867120-49867120
6 PNKP NM_007254.4(PNKP):c.1253_1269dup (p.Thr424fs) Duplication Pathogenic 4847 rs587784365 GRCh37: 19:50365057-50365058
GRCh38: 19:49861800-49861801
7 PNKP NM_007254.4(PNKP):c.1221_1223del (p.Thr408del) Deletion Pathogenic 190219 rs786205207 GRCh37: 19:50365104-50365106
GRCh38: 19:49861847-49861849
8 PNKP NM_007254.4(PNKP):c.1227_1228del (p.Cys409_Glu410delinsTer) Microsatellite Pathogenic 1033198 GRCh37: 19:50365099-50365100
GRCh38: 19:49861842-49861843
9 PNKP NM_007254.4(PNKP):c.1288_1292dup (p.Arg433fs) Duplication Pathogenic 1033199 GRCh37: 19:50365034-50365035
GRCh38: 19:49861777-49861778
10 PNKP NM_007254.4(PNKP):c.1029+2T>C SNV Pathogenic/Likely pathogenic 206401 rs199919568 GRCh37: 19:50365626-50365626
GRCh38: 19:49862369-49862369
11 PNKP NM_007254.4(PNKP):c.896C>T (p.Pro299Leu) SNV Uncertain significance 1027736 GRCh37: 19:50365835-50365835
GRCh38: 19:49862578-49862578
12 PNKP NM_007254.4(PNKP):c.1091G>A (p.Ser364Asn) SNV Uncertain significance 839982 GRCh37: 19:50365477-50365477
GRCh38: 19:49862220-49862220
13 PNKP NM_007254.4(PNKP):c.811G>A (p.Glu271Lys) SNV Uncertain significance 652349 rs1028247558 GRCh37: 19:50366951-50366951
GRCh38: 19:49863694-49863694
14 PNKP NM_007254.4(PNKP):c.1559A>G (p.Glu520Gly) SNV Uncertain significance 285527 rs886043128 GRCh37: 19:50364512-50364512
GRCh38: 19:49861255-49861255
15 PNKP NM_007254.4(PNKP):c.1389T>G (p.Phe463Leu) SNV Uncertain significance 560654 rs763116781 GRCh37: 19:50364765-50364765
GRCh38: 19:49861508-49861508
16 PNKP NM_007254.4(PNKP):c.1003G>A (p.Gly335Ser) SNV Uncertain significance 582794 rs768567927 GRCh37: 19:50365654-50365654
GRCh38: 19:49862397-49862397
17 PNKP NM_007254.4(PNKP):c.670C>T (p.Arg224Cys) SNV Uncertain significance 206391 rs761117623 GRCh37: 19:50367295-50367295
GRCh38: 19:49864038-49864038
18 PNKP NM_007254.4(PNKP):c.416G>A (p.Arg139His) SNV Uncertain significance 159794 rs34472250 GRCh37: 19:50368466-50368466
GRCh38: 19:49865209-49865209
19 PNKP NM_007254.4(PNKP):c.901C>T (p.Arg301Trp) SNV Uncertain significance 95491 rs201503405 GRCh37: 19:50365830-50365830
GRCh38: 19:49862573-49862573
20 PNKP NM_007254.4(PNKP):c.131G>A (p.Arg44Gln) SNV Uncertain significance 568677 rs1568663138 GRCh37: 19:50370331-50370331
GRCh38: 19:49867074-49867074
21 PNKP NM_007254.4(PNKP):c.1003G>T (p.Gly335Cys) SNV Uncertain significance 206399 rs768567927 GRCh37: 19:50365654-50365654
GRCh38: 19:49862397-49862397
22 PNKP NM_007254.4(PNKP):c.1052C>T (p.Pro351Leu) SNV Uncertain significance 587403 rs797045891 GRCh37: 19:50365516-50365516
GRCh38: 19:49862259-49862259
23 PNKP NM_007254.4(PNKP):c.1430T>C (p.Met477Thr) SNV Uncertain significance 565845 rs766655539 GRCh37: 19:50364724-50364724
GRCh38: 19:49861467-49861467
24 PNKP NM_007254.4(PNKP):c.1381A>G (p.Asn461Asp) SNV Uncertain significance 409614 rs775762473 GRCh37: 19:50364870-50364870
GRCh38: 19:49861613-49861613

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

72
# Symbol AA change Variation ID SNP ID
1 PNKP p.Gly375Trp VAR_073369 rs786203983

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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7 CNVD
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11 DGIdb
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61 PubMed
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71 UMLS via Orphanet
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