Novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene associated with 46,XY primary amenorrhea.

Objective To determine the genetic cause of 46,XY primary amenorrhea in three 46,XY girls. Design Whole exome sequencing. Setting University cytogenetics center. Patient(s) Three patients with unexplained 46,XY primary amenorrhea were included in the study. Intervention(s) Potentially pathogenic variants were confirmed by Sanger sequencing, and familial segregation was determined where parents' DNA was available. Main Outcome Measure(s) Exome sequencing was performed in the three patients, and the data were analyzed for potentially pathogenic mutations. The functional consequences of mutations were predicted. Result(s) Three novel homozygous nonsense mutations in the luteinizing hormone receptor ( LHCGR ) gene were identified:c.1573 C→T, p.Gln525Ter, c.1435 C→T p.Arg479Ter, and c.508 C→T, p.Gln170Ter. Conclusion(s) Inactivating mutations of the LHCGR gene may be a more common cause of 46,XY primary amenorrhea than previously considered.