title: Mutation screening of SEMA3A and SEMA7A in patients with congenital hypogonadotropic hypogonadism.
abstract: BACKGROUND
  Congenital hypogonadotropic hypogonadism (HH), a rare disorder characterized by absent, partial, or delayed puberty, can be caused by the lack or deficient number of hypothalamic gonadotropin-releasing hormone (GnRH) neurons. SEMA3A was recently implicated in the etiology of the disorder, and Sema7A-deficient mice have a reduced number of GnRH neurons in their brains.
  
  
  METHODS
  SEMA3A and SEMA7A were screened by Sanger sequencing in altogether 50 Finnish HH patients (34 with Kallmann syndrome (KS; HH with hyposmia/anosmia) and 16 with normosmic HH (nHH)). In 20 patients, mutation(s) had already been found in genes known to be implicated in congenital HH.
  
  
  RESULTS
  Three heterozygous variants (c.458A>G (p.Asn153Ser), c.1253A>G (p.Asn418Ser), and c.1303G>A (p.Val435Ile)) were found in SEMA3A in three KS patients, two of which also had a mutation in FGFR1. Two rare heterozygous variants (c.442C>T (p.Arg148Trp) and c.1421G>A (p.Arg474Gln)) in SEMA7A were found in one male nHH patient with a previously identified KISS1R nonsense variant and one male KS patient with a previously identified mutation in KAL1, respectively.
  
  
  CONCLUSIONS
  Our results suggest that heterozygous missense variants in SEMA3A and SEMA7A may modify the phenotype of KS but most likely are not alone sufficient to cause the disorder.
authors: 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors: Johanna
authors: J
authors: Känsäkoski
authors: 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
authors: Rainer
authors: R
authors: Fagerholm
authors: Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors: Eeva-Maria
authors: EM
authors: Laitinen
authors: 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors: Kirsi
authors: K
authors: Vaaralahti
authors: Department of Medical Genetics, Folkhälsan Institute of Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Peter
authors: P
authors: Hackman
authors: Service of Endocrinology, Diabetes and Metabolism, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors: Nelly
authors: N
authors: Pitteloud
authors: 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors: Taneli
authors: T
authors: Raivio
authors: 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors: Johanna
authors: J
authors: Tommiska
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland; D058851:GPI-Linked Proteins / Q000235:genetics; D014644:Genetic Variation; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000151:congenital* / Q000235:genetics*; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D040121:Semaphorin-3A / Q000235:genetics*; D039961:Semaphorins / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; C108639:SEMA3A protein, human; C118753:SEMA7A protein, human; D040121:Semaphorin-3A; D039961:Semaphorins; D007987:Gonadotropin-Releasing Hormone