Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism

Abstract Background Isolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin‐releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2...

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Autores principales:	Meichao Men, Dan‐Na Chen, Jia‐Da Li, Xinying Wang, Wang Zeng, Fang Jiang, Ruizhi Zheng, Wenting Dai
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	idiopathic hypogonadotropic hypogonadism NRP1 NRP2 PLXNA1 whole exome sequencing Genetics QH426-470
Acceso en línea:	https://doaj.org/article/7380da4e170b472ea1731bbcf0fa60da
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spelling	oai:doaj.org-article:7380da4e170b472ea1731bbcf0fa60da2021-11-21T19:38:53ZAnalysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism2324-926910.1002/mgg3.1816https://doaj.org/article/7380da4e170b472ea1731bbcf0fa60da2021-11-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1816https://doaj.org/toc/2324-9269Abstract Background Isolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin‐releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2 and PLXNA to participate in axonal projection, dendritic branching, synaptic formation, and neuronal migration. Deficiency in SEMA3A, NRP1, NRP2, and PLXNA1 have been related to abnormal GnRH neuron development in mice and IHH in humans. Methods The aim of this study was to examine the genotypic and phenotypic spectra of the NRP1, NRP2, and PLXNA1 genes in a large cohort of IHH probands from China. We screened NRP1, NRP2, and PLXNA1 variants in Chinese IHH patients by whole exome sequencing and pedigree analysis. Results We identified 10 heterozygous missense variants in PLXNA1, five heterozygous missense variants in NRP1, and two heterozygous missense variants in NRP2. NRP1 variants were found only in IHH patients with defective olfaction (i.e., Kallmann syndrome, KS). In addition, 85% (17/20) of patients harbored variants in other IHH‐associated genes. Conclusion Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2 genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss.Meichao MenDan‐Na ChenJia‐Da LiXinying WangWang ZengFang JiangRuizhi ZhengWenting DaiWileyarticleidiopathic hypogonadotropic hypogonadismNRP1NRP2PLXNA1whole exome sequencingGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	idiopathic hypogonadotropic hypogonadism NRP1 NRP2 PLXNA1 whole exome sequencing Genetics QH426-470
spellingShingle	idiopathic hypogonadotropic hypogonadism NRP1 NRP2 PLXNA1 whole exome sequencing Genetics QH426-470 Meichao Men Dan‐Na Chen Jia‐Da Li Xinying Wang Wang Zeng Fang Jiang Ruizhi Zheng Wenting Dai Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
description	Abstract Background Isolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin‐releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2 and PLXNA to participate in axonal projection, dendritic branching, synaptic formation, and neuronal migration. Deficiency in SEMA3A, NRP1, NRP2, and PLXNA1 have been related to abnormal GnRH neuron development in mice and IHH in humans. Methods The aim of this study was to examine the genotypic and phenotypic spectra of the NRP1, NRP2, and PLXNA1 genes in a large cohort of IHH probands from China. We screened NRP1, NRP2, and PLXNA1 variants in Chinese IHH patients by whole exome sequencing and pedigree analysis. Results We identified 10 heterozygous missense variants in PLXNA1, five heterozygous missense variants in NRP1, and two heterozygous missense variants in NRP2. NRP1 variants were found only in IHH patients with defective olfaction (i.e., Kallmann syndrome, KS). In addition, 85% (17/20) of patients harbored variants in other IHH‐associated genes. Conclusion Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2 genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss.
format	article
author	Meichao Men Dan‐Na Chen Jia‐Da Li Xinying Wang Wang Zeng Fang Jiang Ruizhi Zheng Wenting Dai
author_facet	Meichao Men Dan‐Na Chen Jia‐Da Li Xinying Wang Wang Zeng Fang Jiang Ruizhi Zheng Wenting Dai
author_sort	Meichao Men
title	Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
title_short	Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
title_full	Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
title_fullStr	Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
title_full_unstemmed	Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
title_sort	analysis of plxna1, nrp1, and nrp2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/7380da4e170b472ea1731bbcf0fa60da
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Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism

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