Abstract
The etiology of most cases of 46,XY gonadal dysgenesis in the absence
of extragenital anomalies is not accounted for by mutations in the
genes known to date to be involved in sex determination. We have
investigated the possibility that mutations in the gene
LHX9, whose murine ortholog causes isolated gonadal
agenesis when inactivated, might be responsible for gonadal dysgenesis
and agenesis in humans. We isolated a human LHX9
complementary DNA (cDNA), mapped the gene to the long arm of human
chromosome 1, and determined its genomic structure. We found that
LHX9 is highly conserved between species, sharing in
particular over 98% amino acid identity. A mutational screen was
performed in a sample of patients with a range of gonadal
maldevelopment, including bilateral gonadal agenesis in two sisters
with an opposite sex karyotype. We did not detect mutations in the open
reading frame of LHX9 in the patients studied. However,
the extent of between-species structural conservation suggests that
LHX9 deserves further consideration as a determinant of
gonadal function in humans.