Introduction:
46,XY gonadal dysgenesis (GD) is one kind of disorders of sex development (DSD) caused by alterations occurring at the process of gonadal determination, which requires coordinated expression and regulation of many genes(1). The clinical features of 46,XY GD ranged from 46,XY partial gonadal dysgenesis (PGD) to 46,XY complete gonadal dysgenesis (CGD). Genetic heterogeneity for 46,XY GD has been demonstrated in recent studies. A number of chromosomal structural aberrations and gene mutations have been found to be associated with 46,XY GD, such as 9p24.3 deletion, Xp21.2 duplication, 10q26.1 deletion, mutation of SRY, SOX9, DHH, DMRT1 and NR5A1 genes(2, 3). About 20-30% 46,XY gonadal dysgenesis patients have mutations in SRY or NR5A1 gene(4).
The DMRT1 (Doublesex and mab-3 related transcription factor 1) gene encodes a male-specific transcriptional regulator with a conserved zinc finger-like DNA-binding domain which plays an important role in sex determination and differentiation by controlling testis development and male germ cell proliferation (5, 6). The deletions and mutations of DMRT1 gene have been reported to cause 46,XY GD(7, 8). Here, we identified a homozygous DMRT1 mutation c.967G>A (p.Val323Ile) in a Chinese patient of CGD, to the best of our knowledge, this is the first case of homozygous mutation in the DMRT1 gene which could provide insight into the disease-causing mechanism by a hypomorphic mutation in an autosomal recessive pattern.