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.