NM_001376.4(DYNC1H1):c.10151G>A (p.Arg3384Gln) AND Mental retardation, autosomal dominant 13

Clinical significance:Pathogenic (Last evaluated: Jun 1, 2013)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000049271.3

Allele description [Variation Report for NM_001376.4(DYNC1H1):c.10151G>A (p.Arg3384Gln)]

NM_001376.4(DYNC1H1):c.10151G>A (p.Arg3384Gln)

Gene:
DYNC1H1:dynein cytoplasmic 1 heavy chain 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q32.31
Genomic location:
Preferred name:
NM_001376.4(DYNC1H1):c.10151G>A (p.Arg3384Gln)
HGVS:
  • NC_000014.9:g.102033136G>A
  • NG_008777.1:g.73609G>A
  • NM_001376.4:c.10151G>A
  • NP_001367.2:p.Arg3384Gln
  • NC_000014.8:g.102499473G>A
  • Q14204:p.Arg3384Gln
Protein change:
R3384Q; ARG3384GLN
Links:
UniProtKB: Q14204#VAR_070587; OMIM: 600112.0008; dbSNP: 397509411
NCBI 1000 Genomes Browser:
rs397509411
Molecular consequence:
  • NM_001376.4:c.10151G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mental retardation, autosomal dominant 13 (MRD13)
Synonyms:
MENTAL RETARDATION, AUTOSOMAL DOMINANT, 13, WITH NEURONAL MIGRATION DEFECTS
Identifiers:
MedGen: C3281202; OMIM: 614563

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000077528OMIMno assertion criteria providedPathogenic
(Jun 1, 2013)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly.

Poirier K, Lebrun N, Broix L, Tian G, Saillour Y, Boscheron C, Parrini E, Valence S, Pierre BS, Oger M, Lacombe D, Geneviève D, Fontana E, Darra F, Cances C, Barth M, Bonneau D, Bernadina BD, N'guyen S, Gitiaux C, Parent P, des Portes V, et al.

Nat Genet. 2013 Jun;45(6):639-47. doi: 10.1038/ng.2613. Epub 2013 Apr 21. Erratum in: Nat Genet. 2013 Aug;45(8):962.

PubMed [citation]
PMID:
23603762
PMCID:
PMC3826256

Details of each submission

From OMIM, SCV000077528.2

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

Description

In a 10-year-old patient (P217) with MRD13 with neuronal migration defects (614563), Poirier et al. (2013) identified a de novo heterozygous c.10151G-A transition in the DYNC1H1 gene, resulting in an arg3384-to-gln (R3384Q) substitution at a conserved residue in the microtubule-binding domain. In vitro functional expression studies showed that the mutant protein had decreased microtubule binding affinity compared to wildtype. The patient had microcephaly (-4 SD), early-onset epilepsy, foot deformities consistent with an axonal neuropathy, and was bedridden with spastic tetraplegia. Brain MRI showed posterior pachygyria, frontal polymicrogyria, dysmorphic basal ganglia and corpus callosum, and hypoplasia of the brainstem and cerebellum.

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

Last Updated: Sep 15, 2017