PLXNB1 mutations in the etiology of idiopathic hypogonadotropic hypogonadism.
PLXNB1
hypogonadotropic hypogonadism
puberty
Journal
Journal of neuroendocrinology
ISSN: 1365-2826
Titre abrégé: J Neuroendocrinol
Pays: United States
ID NLM: 8913461
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
15
02
2022
received:
20
01
2022
accepted:
28
01
2022
pubmed:
17
2
2022
medline:
28
4
2022
entrez:
16
2
2022
Statut:
ppublish
Résumé
Idiopathic hypogonadotropic hypogonadism (IHH) comprises a group of rare genetic disorders characterized by pubertal failure caused by gonadotropin-releasing hormone (GnRH) deficiency. Genetic factors involved in semaphorin/plexin signaling have been identified in patients with IHH. PlexinB1, a member of the plexin family receptors, serves as the receptor for semaphorin 4D (Sema4D). In mice, perturbations in Sema4D/PlexinB1 signaling leads to improper GnRH development, highlighting the importance of investigating PlexinB1 mutations in IHH families. In total, 336 IHH patients (normosmic IHH, n = 293 and Kallmann syndrome, n = 43) from 290 independent families were included in the present study. Six PLXNB1 rare sequence variants (p.N361S, p.V608A, p.R636C, p.V672A, p.R1031H, and p.C1318R) are described in eight normosmic IHH patients from seven independent families. These variants were examined using bioinformatic modeling and compared to mutants reported in PLXNA1. Based on these analyses, the variant p.R1031H was assayed for alterations in cell morphology, PlexinB1 expression, and migration using a GnRH cell line and Boyden chambers. Experiments showed reduced membrane expression and impaired migration in cells expressing this variant compared to the wild-type. Our results provide clinical, genetic, molecular/cellular, and modeling evidence to implicate variants in PLXNB1 in the etiology of IHH.
Substances chimiques
Nerve Tissue Proteins
0
PLXNB1 protein, human
0
Plxnb1 protein, mouse
0
Receptors, Cell Surface
0
Gonadotropin-Releasing Hormone
33515-09-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13103Subventions
Organisme : Intramural NIH HHS
ID : ZIA NS002824
Pays : United States
Informations de copyright
© 2022 British Society for Neuroendocrinology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
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