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NM_139058.3(ARX):c.998C>A (p.Thr333Asn) AND Corpus callosum agenesis-abnormal genitalia syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 1, 2012
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000011951.9

Allele description [Variation Report for NM_139058.3(ARX):c.998C>A (p.Thr333Asn)]

NM_139058.3(ARX):c.998C>A (p.Thr333Asn)

Gene:
ARX:aristaless related homeobox [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp21.3
Genomic location:
Preferred name:
NM_139058.3(ARX):c.998C>A (p.Thr333Asn)
HGVS:
  • NC_000023.11:g.25012997G>T
  • NG_008281.1:g.7952C>A
  • NM_139058.3:c.998C>AMANE SELECT
  • NP_620689.1:p.Thr333Asn
  • NC_000023.10:g.25031114G>T
  • NM_139058.2:c.998C>A
  • Q96QS3:p.Thr333Asn
Protein change:
T333N; THR333ASN
Links:
UniProtKB: Q96QS3#VAR_033261; OMIM: 300382.0015; dbSNP: rs104894745
NCBI 1000 Genomes Browser:
rs104894745
Molecular consequence:
  • NM_139058.3:c.998C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Corpus callosum agenesis-abnormal genitalia syndrome
Synonyms:
Proud Levine Carpenter syndrome; New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum; ACC with abnormal genitalia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010224; MedGen: C0796124; Orphanet: 2508; OMIM: 300004

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000032185OMIM
no assertion criteria provided
Pathogenic
(Feb 1, 2012) 		germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum.

Proud VK, Levine C, Carpenter NJ.

Am J Med Genet. 1992 Apr 15-May 1;43(1-2):458-66.

PubMed [citation]
PMID:
1605226

Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation.

Kato M, Das S, Petras K, Kitamura K, Morohashi KI, Abuelo DN, Barr M, Bonneau D, Brady AF, Carpenter NJ, Cipero KL, Frisone F, Fukuda T, Guerrini R, Iida E, Itoh M, Lewanda AF, Nanba Y, Oka A, Proud VK, Saugier-Veber P, Schelley SL, et al.

Hum Mutat. 2004 Feb;23(2):147-159. doi: 10.1002/humu.10310.

PubMed [citation]
PMID:
14722918
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000032185.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In affected members of the family reported by Proud et al. (1992) in which 3 males had X-linked mental retardation, agenesis of the corpus callosum, and abnormal genitalia (300004), Kato et al. (2004) identified a 998C-A transversion in exon 2 of the ARX gene, resulting in a thr333-to-asn (T333N) mutation. Two female mutation carriers were less severely impaired, but had spastic quadriplegia and seizures. One obligate carrier was retarded with emotional problems, whereas another obligate carrier and her daughter were clinically normal. The authors noted that these findings were consistent with X-linked inheritance with variable expression in females.

In in vitro studies, Cho et al. (2012) found that the mutant T333N protein bound DNA with lower affinity than wildtype ARX, but also had significantly decreased transcriptional repression activity compared to wildtype ARX.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 9, 2023