Population frequency and age of mutation G5741→A in gene NBAS which is a cause of SOPH syndrome in Sakha (Yakutia) Republic

SOPH syndrome (Short stature with Optic nerve atrophy and Pelger–Huet anomaly syndrome, OMIM#614800) is an autosomal recessive hereditary disease characterized by the following main clinical symptoms: postnatal hypoplasia, proportionately short stature, facial dysmorphism, micromelia of feet and hands, limp and loose skin, optic nerve atrophy, and Pelger–Huet anomaly of neutrophils. For the first time, this disease was described in Yakuts. The molecular-genetic study showed that its cause in Yakuts is mutation G5741→A in gene NBAS. On the basis of disequilibrium analysis for linkage of ten microsatellite markers flanking the NBAS gene with the disease, the haplotype of the founder chromosome was determined. The age of the mutation in Yakutia was estimated to be about 804 ± 140 years. The frequency of heterozygous carriers of mutation G5741→A (R1914H) in gene NBAS was found, which averaged 13 per 1000 healthy Yakuts.