A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

Abstract

Desbuquois dysplasia (DBQD) is a severe skeletal dysplasia of autosomal recessive inheritance. DBQD is classified into types 1 and 2 based on presence or absence of hand anomalies. In a previous study, we found a CANT1 (for calcium-activated nucleotidase 1) mutation, c.676G4A in five DBQD families. They were all East Asians (Japanese or Korean). The high prevalence of the same mutation among Japanese and Korean suggested that it is a common founder mutation in the two populations. To examine a possible common founder, we examined the region around CANT1 in chromosomes with c.676G4A mutation by genotyping polymorphic markers in the region for the families. We examined their haplotypes using the family data. We identified in all families a common haplotype containing the CANT1 mutation that ranged up to 550 kb. The two unrelated carriers of the mutation in general populations in Korea and Japan could also have the haplotype. We estimated the age of the founder mutation as B1420 years (95% CI¼880-1940 years). The c.676G4A mutation of CANT1 commonly seen in Japanese and Korean DBQD should be derived from a common founder.

MED resulting from recessively inherited mutations in the gene encoding calcium‐activated nucleotidase CANT1

“…Homozygosity for the p.Val226Met mutation has been reported in one DBQD Kim family, but radiographic data for a full comparison of the phenotype with the case reported here have not been published (Furuichi et al, ; Kim et al, ). Prior to this study the p.Val226Met variant has only been identified in individuals of Japanese and Korean ethnicity (Dai et al, ; Furuichi et al, ). As the MED family was of Latino ancestry, the same mutation may have occurred independently in this ethnic group.…”

Ca2+-activated Nucleotidase 1, a Novel Target Gene for the Transcriptional Repressor DREAM (Downstream Regulatory Element Antagonist Modulator), Is Involved in Protein Folding and Degradation

“…Inclusion bodies containing proteinaceous material within distended ER cisternae have been found in fibroblasts from patients suggesting the possibility of a role for CANT1 in the endochondral ossification pro-cess (23,(57)(58)(59). One report, actually, postulated that the CANT1 deficiency might interfere with the availability of UDPsugars needed for proteoglycan synthesis, but no demonstration was provided (23).…”

“…As for the results on CANT1, their interest is greatly heightened by recent findings showing that nonsense or missense mutations in its gene have been found in a number of cases of severe type 1 and 2 Desbuquois dysplasia, an autosomal recessive chondrodysplasia characterized by severe prenatal and postnatal growth retardation, joint laxity, short extremities, and progressive scoliosis (23,56,57). Inclusion bodies containing proteinaceous material within distended ER cisternae have been found in fibroblasts from patients suggesting the possibility of a role for CANT1 in the endochondral ossification pro-cess (23,(57)(58)(59).…”

Founder Haplotype Analysis of Fanconi Anemia in the Korean Population Finds Common Ancestral Haplotypes for a FANCG Variant

“…Taking into account geographic, historical, and migratory events, FANCG founder mutations in Korean and Japanese FA patients may be shared among other ethnic FA patients descended from northern Mongoloids. Several previous studies between Koreans and Japanese have supported closer genetic similarities than those between other East Asian populations (Nonaka et al, 2007;Ichida et al, 2008;Dai et al, 2011;Hwang et al, 2011;Chiu et al, 2012).…”