NM_130468.3(CHST14):c.878A>G (p.Tyr293Cys) AND Ehlers-Danlos syndrome, musculocontractural type

Significance: Pathogenic
ClinVar: RCV000002429

Variant: NM_130468.3(CHST14):c.878A>G (p.Tyr293Cys)

Type: Variant
Allele: NM_130468.3(CHST14):c.878A>G (p.Tyr293Cys) 17378
Type: single nucleotide variant
Location: Chr15: 40764290 - assembly GRCh37
Chr15: 40472091 - assembly GRCh38
References: dbSNP: 121908258
OMIM: 608429.0004
UniProtKB/Swiss-Prot: VAR_063757
UniProtKB: Q8NCH0#VAR_063757


Disease: Ehlers-Danlos syndrome, musculocontractural type


    In 2 Japanese brothers with adducted thumbs, clubfeet, and progressive joint and skin laxity (EDSMC1; 601776), originally described by Sonoda and Kouno (2000), Dundar et al. (2009) identified homozygosity for an 878A-G transition in the CHST14 gene, resulting in a tyr293-to-cys (Y293C) substitution. Studies in transfected HEK293/T cells showed only the predominant 55-kD species but not the minor 44-kD species seen with wildtype, and no significant amount of D4ST1 was detected in the medium, suggesting degradation of the mutant before reaching the Golgi.
PMID:10766984, PMID:20004762
    In 2 probands from unrelated consanguineous Japanese families with bilateral thumb adduction, clubfeet, and progressive joint and skin laxity, Miyake et al. (2010) identified compound heterozygosity for the same Y293C mutation and the P281L mutation (608429.0005) in the CHST14 gene. The mutations were not detected in 376 Japanese control individuals.