Molecular diagnostics of disorders of sex development

Abstract

Objective To elucidate the molecular pathogenesis of DSD and exploring the possibility of its molecular diagnostics. Methods Genomic DNA was extracted from peripheral blood samples from 22 DSD patients.Five samples were detected by CMA while genomic DNA of other samples was analyzed by whole exome sequencing.And positive variants and parental blood samples were verified by Sanger sequencing. Results Among 6 novel mutations, 1 duplication upstream of SOX9 in chromosome 17(Chr17: 70, 117, 161-70, 122, 560) with ovotesticular DSD was identified by CMA and 5 genetic mutations by whole exome sequencing and verified by Sanger sequencing.There were 5 each of missense mutation(c.871T>G, p.W291G)in DAX1 with congenital adrenal hypoplasia, nonsense mutation(c.292+ 1G>A, c.293-13A/C>G)in CYP21A2 with congenital adrenal hyperplasia, frameshift mutation(c.2916_ 2917delGT; p. Gln972 HisfsX22)in CDH7 with CHARGE syndrome, missense mutation (c.2612C>T; p. Ala871Val) and missense mutation (c.528C>A; p. Ser176 Arg) in AR with androgen insensitivity syndrome. Conclusions Genetic diagnosis via CMA and whole exome sequencing is feasible for DSD patients.Thus it provides rationales for clinical diagnosis of other diseases. Key words: Disorders of sex development; Gene chip; DNA sequencing