title: Nasal embryonic LHRH factor (NELF) mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome.
abstract: OBJECTIVE
  To determine if mutations in NELF, a gene isolated from migratory GnRH neurons, cause normosmic idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS).
  
  
  METHODS
  Molecular analysis correlated with phenotype.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  A total of 168 IHH/KS patients as well as unrelated control subjects were studied for NELF mutations.
  
  
  METHODS
  NELF coding regions/splice junctions were subjected to polymerase chain reaction (PCR)-based DNA sequencing. Eleven additional IHH/KS genes were sequenced in three patients with NELF mutations.
  
  
  METHODS
  Mutations were confirmed by sorting intolerant from tolerant, reverse-transcription (RT)-PCR, and Western blot analysis.
  
  
  RESULTS
  Three novel NELF mutations absent in 372 ethnically matched control subjects were identified in 3/168 (1.8%) IHH/KS patients. One IHH patient had compound heterozygous NELF mutations (c.629-21G>C and c.629-23C>G), and he did not have mutations in 11 other known IHH/KS genes. Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/KAL1 (c.757G>A; p.Ala253Thr of NELF and c.488_490delGTT; p.Cys163del of KAL1) and NELF/TACR3 (c.1160-13C>T of NELF and c.824G>A; p.Trp275X of TACR3). In vitro evidence of these NELF mutations included reduced protein expression and splicing defects.
  
  
  CONCLUSIONS
  Our findings suggest that NELF is associated with normosmic IHH and KS, either singly or in combination with a mutation in another gene.
authors.affiliation: Section of Reproductive Endocrinology, Infertility, and Genetics, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Bhagavath
authors.forename: Sung-Gyu
authors.initials: SG
authors.lastname: Cho
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Ha
authors.forename: Irene
authors.initials: I
authors.lastname: Meliciani
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wenzel
authors.forename: Robert H
authors.initials: RH
authors.lastname: Podolsky
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Chorich
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Stackhouse
authors.forename: Anna M H
authors.initials: AM
authors.lastname: Grove
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Odom
authors.forename: Metin
authors.initials: M
authors.lastname: Ozata
authors.forename: David P
authors.initials: DP
authors.lastname: Bick
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sherins
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cameron
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000235:genetics*; D017436:Kallmann Syndrome / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C411985:NSMF protein, human; D014157:Transcription Factors