Поиск мутаций в генах PAX3 , MITF , SOX10 и SNAI2 при синдроме Ваарденбурга в Якутии

Abstract

The Waardenburg syndrome (WS) is a rare autosomal dominant disease with varying phenotypic manifestations and heterogeneous genetic control characterized by hearing loss and pigmentation impairments of skin, hair and iris. 514 patients with congenital hearing impairments from 484 families were examined in the Sakha Republic of Russia and three patients with phenotypes corresponding to the WS from two families were identified, thus, the frequency of the WS among patients with congenital hearing impairments in the Sakha Republic is 0.62% (3/484). To search the molecular genetics causes of the WS in these patients Sanger sequencing of the coding fragments of genes PAX3 , MITF , SOX10 and SNAI2 was performed. The synonymous heterozygous substitutions were found in two members of one family with WS type I: in daughter - c.804C>T (p.Asn268Asn) in gene PAX3 and in her father - c.927C>T (p.His309His) in gene SOX10 . Both variants c.804C>T (p.Asn268Asn) and c.927C>T (p.His309His) are likely not pathogenic. Heterozygous transition c.772C>T in exon 8 of gene MITF, previously known in association with the WS, was found in one patient with the WS type II. The c.772C>T variant leads to premature stop codon (p.Arg259*) terminating translation of MITF. A patient with a nonsense variant c.772C>T (p.Arg259*) in gene MITF was characterized by a rare phenotype of the WS type II: congenital unilateral hearing loss (deafness in left ear, normal hearing in right ear) and unilateral heterochromia of irises (dark brown right eye, brilliant blue left eye). The results confirm the association of the MITF mutations with the WS type II and expand the information on phenotypic variability of this syndrome.