Mutational Analysis of the LHX1 Gene in a French National Cohort of Patients with Mayer-Rokitansky-Küster-Hauser Syndrome

Mutational Analysis of the LHX1 Gene in a French National Cohort of Patients with Mayer-Rokitansky-Küster-Hauser Syndrome

Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome) is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal secondary sexual characteristics development and a normal 46, XX karyotype. MRKH syndrome is a cause of primary amenorrhea with an incidence of approximately 1 in 5,000 newborn girls. Most cases of MRKH syndrome are sporadic, but some familial cases have been reported, suggesting a genetic cause. The genetic basis of MRKH syndrome remains largely unknown and seems heterogeneous. The LHX1 gene has been suggested to be a strong candidate, because (i) inactivation of the ortholog gene (Lim1) in the mouse model causes a Müllerian aplasia, and (ii) it is located in the chromosomal region 17q12, where deletions including this gene have been identified in approximately 5% of MRKH patients. Recently, three relevant heterozygous mutations of the LHX1 gene have been reported in association with the syndrome.