NM_001885.2(CRYAB):c.60delC (p.Pro20=fs) AND Alpha-B crystallinopathy

Clinical significance:Pathogenic (Last evaluated: Aug 7, 2013)

Review status:(2/4)2 stars out of maximum of 4 stars

classified by multiple submitters

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000043523.26

Allele description [Variation Report for NM_001885.2(CRYAB):c.60delC (p.Pro20=fs)]

Gene:
CRYAB:crystallin, alpha B [Gene - OMIM]
Variant type:
Deletion
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_001885.2(CRYAB):c.60delC (p.Pro20=fs)
HGVS:
  • NC_000011.10:g.111911665delG
  • NG_009824.2:g.17058delC
  • NG_033080.1:g.3930delG
  • NM_001541.3:c.-1165delG
  • NM_001885.2:c.60delC
  • NP_001876.1:p.Ser21Alafs
  • NC_000011.9:g.111782389delG
  • NG_009824.1:g.5085delC
  • NM_001885.1:c.60delC
  • NP_001876.1:p.Pro20=fs
Links:
GeneReviews: NBK1499; OMIM: 123590.0005; dbSNP: 281865141
NCBI 1000 Genomes Browser:
rs281865141
Molecular consequence:
  • NM_001541.3:c.-1165delG - 2KB upstream variant - [Sequence Ontology: SO:0001636]
  • NM_001885.2:c.60delC - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Alpha-B crystallinopathy (MFM2)
Synonyms:
MYOPATHY, DESMIN-RELATED, ASSOCIATED WITH MUTATION IN THE CRYAB GENE; MYOPATHY, MYOFIBRILLAR, ALPHA-B CRYSTALLIN-RELATED; MYOPATHY, MYOFIBRILLAR, WITH OR WITHOUT CATARACT AND/OR CARDIOMYOPATHY; See all synonyms [MedGen]
Identifiers:
GeneReviews: NBK1499; MedGen: C1837317; OMIM: 608810; OMIM: 613869; Orphanet: 280553
Age of onset:
Neonatal/infancy
Prevalence:
<1 / 1 000 000 280553

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000043807OMIMPathogenic
(Aug 7, 2013)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000055819GeneReviewspathologic
(Oct 29, 2012)
not providedliterature only

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providednot providednot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives.

Lacson AG, Seshia SS, Sarnat HB, Anderson J, DeGroot WR, Chudley A, Adams C, Darwish HZ, Lowry RB, Kuhn S, et al.

Can J Neurol Sci. 1994 Aug;21(3):203-12.

PubMed [citation]
PMID:
8000975

Infantile muscular dystrophy in Canadian aboriginals is an αB-crystallinopathy.

Del Bigio MR, Chudley AE, Sarnat HB, Campbell C, Goobie S, Chodirker BN, Selcen D.

Ann Neurol. 2011 May;69(5):866-71. doi: 10.1002/ana.22331. Epub 2011 Feb 18.

PubMed [citation]
PMID:
21337604
PMCID:
PMC3085857

Details of each submission

From OMIM, SCV000043807.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 8 patients with fatal infantile hypertonic myofibrillar myopathy (613869), including 3 reported by Lacson et al. (1994), Del Bigio et al. (2011) identified the same homozygous 1-bp deletion in the CRYAB gene (123590.0005), resulting in a ser21-to-ala (S21A) change and a stop codon after 23 missense residues. All patients were Canadian aboriginals of Cree descent, consistent with a founder effect. The phenotype was characterized by onset in the first weeks of life of rapidly progressive muscular rigidity of the trunk and limbs associated with increasing respiratory difficulty resulting in death before age 3 years. Muscle biopsies showed dystrophic changes, endomysial fibrosis, eosinophilic deposits, and Z-band streaming. Immunohistochemistry using an antibody against the full-length CRYAB protein showed absence of staining, but an antibody against the first 10 residues of the protein showed some residual staining. Heterozygous parents were unaffected, including 1 mother with mild myopathic symptoms but normal CK levels. Del Bigio et al. (2011) noted that late-onset myofibrillar myopathy (608810) is typically seen in heterozygous individuals; however, in this disease, the parental phenotype may be rescued by limited expression of the 44-amino acid truncated nonfunctional gene product. Del Bigio et al. (2011) postulated that a disruption of CRYAB interaction with titin (TTN; 188840) may contribute to reduced muscle elasticity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From GeneReviews, SCV000055819.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature onlynot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

Last Updated: Aug 17, 2014

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