title: Novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene associated with 46,XY primary amenorrhea.
abstract: To determine the genetic cause of 46,XY primary amenorrhea in three 46,XY girls.
  
  
  
  Whole exome sequencing.
  
  
  
  University cytogenetics center.
  
  
  
  Three patients with unexplained 46,XY primary amenorrhea were included in the study.
  
  
  
  Potentially pathogenic variants were confirmed by Sanger sequencing, and familial segregation was determined where parents' DNA was available.
  
  
  
  Exome sequencing was performed in the three patients, and the data were analyzed for potentially pathogenic mutations. The functional consequences of mutations were predicted.
  
  
  
  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.
  
  
  
  Inactivating mutations of the LHCGR gene may be a more common cause of 46,XY primary amenorrhea than previously considered.
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia; Human Developmental Genetics, Institut Pasteur, Paris, France.
authors.forename: Imen
authors.initials: I
authors.lastname: Ben Hadj Hmida
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Mougou-Zerelli
authors.affiliation: Department of Gynecology and Obstetrics, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Anis
authors.initials: A
authors.lastname: Hadded
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Sarra
authors.initials: S
authors.lastname: Dimassi
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Molka
authors.initials: M
authors.lastname: Kammoun
authors.affiliation: Human Developmental Genetics, Institut Pasteur, Paris, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Bignon-Topalovic
authors.affiliation: Department of Gynecology and Obstetrics, Fattouma Bourguiba Teaching Hospital, Monastir, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bibi
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.affiliation: Human Developmental Genetics, Institut Pasteur, Paris, France.
authors.forename: Anu
authors.initials: A
authors.lastname: Bashamboo
authors.affiliation: Human Developmental Genetics, Institut Pasteur, Paris, France. Electronic address: kenneth.mcelreavey@pasteur.fr.
authors.forename: Ken
authors.initials: K
authors.lastname: McElreavey
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D010641:Phenotype; D011974:Receptors, LH / Q000235:genetics*; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D011974:Receptors, LH
keywords: Exome sequencing; LHCGR mutation; disorders of sex development (DSD); primary amenorrhea