AOA4
MCID: ATX033
MIFTS: 23

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 75 29 6
Aoa4 57 53 59 75
Ataxia-Oculomotor Apraxia Type 4 53 59
Ataxia-Oculomotor Apraxia, Type 4 40
Ataxia-Oculomotor Apraxia-4 53

Characteristics:

Orphanet epidemiological data:

59
ataxia-oculomotor apraxia type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM:

57
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:

32
ataxia-oculomotor apraxia 4:
Onset and clinical course rapidly progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Ataxia-Oculomotor Apraxia 4

OMIM : 57 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 apraxia and astrocytoma. An important gene associated with Ataxia-Oculomotor Apraxia 4 is PNKP (Polynucleotide Kinase 3'-Phosphatase). Affiliated tissues include eye, and related phenotypes are ataxia and tetraplegia

UniProtKB/Swiss-Prot : 75 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 3 family:

Ataxia-Oculomotor Apraxia 4

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

# Related Disease Score Top Affiliating Genes
1 apraxia 10.2
2 astrocytoma 10.2
3 pilocytic astrocytoma 10.2

Symptoms & Phenotypes for Ataxia-Oculomotor Apraxia 4

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Ataxia-Oculomotor Apraxia 4:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 ataxia 32 HP:0001251
2 tetraplegia 32 HP:0002445
3 cognitive impairment 32 occasional (7.5%) HP:0100543
4 peripheral neuropathy 32 HP:0009830
5 dystonia 32 HP:0001332
6 areflexia 32 HP:0001284
7 cerebellar atrophy 32 HP:0001272
8 oculomotor apraxia 32 HP:0000657

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:

41
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

Variations for Ataxia-Oculomotor Apraxia 4

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

75
# 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 14)
# Gene Variation Type Significance SNP ID Assembly Location
1 PNKP NM_007254.3(PNKP): c.1253_1269dupGGGTCGCCATCGACAAC (p.Thr424Glyfs) duplication Pathogenic rs587784365 GRCh38 Chromosome 19, 49861801: 49861817
2 PNKP NM_007254.3(PNKP): c.1253_1269dupGGGTCGCCATCGACAAC (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 rs886037745 GRCh37 Chromosome 19, 50364521: 50364522
12 PNKP NM_007254.3(PNKP): c.1549_1550insTGTACTGC (p.Gln517Leufs) insertion Pathogenic rs886037745 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

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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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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73 UMLS
74 UMLS via Orphanet
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