Mutation screening of SEMA3A and SEMA7A in patients with congenital hypogonadotropic hypogonadism
J Känsäkoski, R Fagerholm, EM Laitinen… - Pediatric …, 2014 - nature.com
J Känsäkoski, R Fagerholm, EM Laitinen, K Vaaralahti, P Hackman, N Pitteloud, T Raivio…
Pediatric research, 2014•nature.comBackground: 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 …
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 …
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.
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.
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