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. (C) 2016 by American Society for Reproductive Medicine.