LHX1 Mutation Screening In Patients With Müllerian Duct Abnormalities Of Unknown Cause

BACKGROUNDS The female reproductive system anomalities include mullerian dysplasias and mullerian improper fusions, such as uterine agenesis, uincornuate uterus, uterus didelphys, bicornuate uterus and septate uterus. The formers are sterile and the latters with pure mediastinal vaginal or double uterus usually cause miscarriage, premature birth or neonate death. However, the genetics etiology of mullerian duct abnormalities (MA) is still unclear, to date only WNT4 mutions are detected in MA patients. LHX1, located in chromosome 17q12 and encodes a member of a large protein family with LIM domain, may function as a transcriptional regulator and be involved in control of differentiation and development of neural and lymphoid cells. Liml-null female mice had ovaries, but they lacked a uterus and oviduct. Recent researchs in MA patients by comparative genomics hybridization and the whole genome analysis found the imbalance or missing on 17q12 where LHX1 gene locates, which imply LHX1 may play important roles in Mullerian duct development.OBJECTIVES To investigate whether or not LHX1 gene mutation existed in Han Chinese patients with Mullerian duct abnormalities of unknown cause.METHODS LHX1 gene 5 exons was sequenced in a group of 96 Han Chinese patients (including 41 patients with incomplete Mullerian fusion,12 MRKH patients,11 primordial uterus,7 infantile uterus and 25 patients with unicornous uterus or rudimentary horn uterus) and 105 control individuals. The objective fragments were PCR-amplificated and sequenced, then compared with the normal sequences in NCBI.RESULTS We have identified c.2066-2077del(p.357-360delPro-Ser) in the Exon5 of LHX1 gene in a double-uterus patient and a control sample.CONCLUSIONS Mutation of LHX1 in coding regions may not be the correlated etiological factors involved in mullerian duct abnormalities in Han Chinese patients. We need more studies to elucidate the genetic etiology of Mullerian duct abnormalities in Chinese individuals. The deletion c.2066-2077del of LHX1 gene is a new rare polymorphism of Han Chinese. Further studies should focus on the relevance of infertility and the deletion.