title: Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism.
abstract: OBJECTIVE
  To determine the frequency of rare nucleotide variants in GNRHR and GPR54 in a large cohort of probands (n = 166) with normosmic idiopathic hypogonadotropic hypogonadism (nIHH), characterized by mode of inheritance, testicular volume, and presence or absence of endogenous LH pulsations.
  
  
  METHODS
  Whenever possible, probands answered detailed questionnaires, underwent full physical exams, and underwent q 10-min frequent blood sampling for LH. Exons segments for GNRHR and GPR54 were screened for mutations. Nucleotide changes were identified as rare variants if they occurred at less than 1% frequency in an ethnically matched control population.
  
  
  RESULTS
  Sixty-two percent of male probands were classified as sporadic, meaning that no other family members had delayed puberty or nIHH. In contrast, 61% of female probands were from familial pedigrees, with either autosomal dominant or autosomal recessive inheritance. Patients displayed a broad spectrum of disease severity based on testicular size and endogenous LH pulsations. Twenty-four rare variants were identified in GNRHR (within 15 probands) and seven rare variants in GPR54 (within five probands).
  
  
  CONCLUSIONS
  Rare variants in GNRHR are more common than GPR54 in a nIHH population.
authors.affiliation: Reproductive Endocrine Unit, Massachusetts General Hospital BHX 504, Fruit Street, Boston, Massachusetts 02114, USA.
authors.forename: Felecia
authors.initials: F
authors.lastname: Cerrato
authors.forename: Jenna
authors.initials: J
authors.lastname: Shagoury
authors.forename: Milena
authors.initials: M
authors.lastname: Kralickova
authors.forename: Andrew
authors.initials: A
authors.lastname: Dwyer
authors.forename: John
authors.initials: J
authors.lastname: Falardeau
authors.forename: Metin
authors.initials: M
authors.lastname: Ozata
authors.forename: Guy
authors.initials: G
authors.lastname: Van Vliet
authors.forename: Pierre
authors.initials: P
authors.lastname: Bouloux
authors.forename: Janet E
authors.initials: JE
authors.lastname: Hall
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Hayes
authors.forename: Nelly
authors.initials: N
authors.lastname: Pitteloud
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Martin
authors.forename: Corrine
authors.initials: C
authors.lastname: Welt
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Seminara
mesh_terms: D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH / Q000235:genetics*
chemical_list: C484844:GNRHR protein, human; C118688:KISS1R protein, human; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH