• PMID: 24522099
• Gene Name: SEMA3A
• Condition: Congenital hypogonadotropic hypogonadism
• Association: The 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.
• PMID: 24522099
• Gene Name: SEMA3A
• Condition: Congenital hypogonadotropic hypogonadism
• Association: The 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
• Mutation: SEMA3A (c.458A>G (p.Asn153Ser), c.1253A>G (p.Asn418Ser), and c.1303G>A (p.Val435Ile)), SEMA7A (c.442C>T (p.Arg148Trp) and c.1421G>A (p.Arg474Gln))
• Population size: 50
• Population details: 50 (34 with Kallmann syndrome (KS; HH with hyposmia/anosmia) and 16 with normosmic HH (nHH))
• Sex: Male
• Infertility type: Male infertility
• Associated genes: SEMA3A, SEMA7A
• Other associated phenotypes: Congenital hypogonadotropic hypogonadism

Mutation screening of SEMA3A and SEMA7A in patients with congenital hypogonadotropic hypogonadism

Känsäkoski J, Fagerholm R, Laitinen EM, Vaaralahti K, Hackman P, Pitteloud N, Raivio T, Tommiska J.

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. CONCLUSION: 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. FAU - Känsäkoski, Johanna AU - Känsäkoski J AD - 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland. FAU - Fagerholm, Rainer AU - Fagerholm R AD - 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland. FAU - Laitinen, Eeva-Maria AU - Laitinen EM AD - Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland. FAU - Vaaralahti, Kirsi AU - Vaaralahti K AD - 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland. FAU - Hackman, Peter AU - Hackman P AD - Department of Medical Genetics, Folkhälsan Institute of Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland. FAU - Pitteloud, Nelly AU - Pitteloud N AD - Service of Endocrinology, Diabetes and Metabolism, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. FAU - Raivio, Taneli AU - Raivio T AD - 1] Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland [2] Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.