Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism.
Analysis of PLXNA1, NRP1, and NRP2 variants in a cohort of patients with isolated hypogonadotropic hypogonadism.
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对一组孤立性低促性腺素性性腺功能减退症患者的 PLXNA1、NRP1 和 NRP2 变异进行分析。
DOI：
10.1002/mgg3.1816
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发表时间：
2021-11
影响因子：
2
通讯作者：
Dai W
中科院分区：
文献类型：
--
作者：
Men M;Chen DN;Li JD;Wang X;Zeng W;Jiang F;Zheng R;Dai W
孤立性低促性腺激素性性腺功能减退症（IHH）是一种临床综合征，表现为继发于促性腺激素释放激素（GnRH）合成、分泌或作用缺陷的性腺功能衰竭。分泌的糖蛋白SEMA 3A结合其受体NRP 1或NRP 2和PLXNA以参与轴突投射、树突分支、突触形成和神经元迁移。SEMA 3A、NRP 1、NRP 2和PLXNA 1的缺乏与小鼠中GnRH神经元发育异常和人类中IHH相关。本研究的目的是在一个来自中国的IHH先证者的大队列中检查NRP 1、NRP 2和PLXNA 1基因的基因型和表型谱。我们通过全外显子组测序和谱系分析在中国IHH患者中筛选了NRP 1、NRP 2和PLXNA 1变体。我们在PLXNA 1中鉴定了10个杂合错义变体，在NRP 1中鉴定了5个杂合错义变体，在NRP 2中鉴定了2个杂合错义变体。NRP 1变体仅在嗅觉缺陷的IHH患者中发现（即，Kallmann综合征，KS）。此外，85%（17/20）的患者在其他IHH相关基因中携带变异。我们的研究极大地丰富了IHH中PLXNA 1、NRP 1和NRP 2的基因型和表型谱。这可能有助于PLXNA 1、NRP 1和NRP 2基因突变的IHH的遗传咨询、诊断和治疗。此外，我们的结果表明NRP 1与听力损失密切相关。我们的研究极大地丰富了IHH中PLXNA 1、NRP 1和NRP 2的基因型和表型谱。这可能有助于PLXNA 1、NRP 1和NRP 2基因突变的IHH的遗传咨询、诊断和治疗。此外，我们的研究结果表明，NRP 1与听力损失密切相关（2/8人）。
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. 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. 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. 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. Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may 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 (2/8 individuals).
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影响因子：
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作者：
Hanchate NK;Giacobini P;Lhuillier P;Parkash J;Espy C;Fouveaut C;Leroy C;Baron S;Campagne C;Vanacker C;Collier F;Cruaud C;Meyer V;García-Piñero A;Dewailly D;Cortet-Rudelli C;Gersak K;Metz C;Chabrier G;Pugeat M;Young J;Hardelin JP;Prevot V;Dodé C
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作者：
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作者：
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通讯作者：
Ruhrberg, Christiana
中国卡尔曼综合征患者 SOX10 突变的功能分析
影响因子：
3.5
作者：
Dai, Wenting;Wu, Jiayu;Li, Jia-Da
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Li, Jia-Da
DOI：
10.1038/s41436-020-01087-5
发表时间：
2021-06
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Kotan LD;Ternier G;Cakir AD;Emeksiz HC;Turan I;Delpouve G;Kardelen AD;Ozcabi B;Isik E;Mengen E;Cakir EDP;Yuksel A;Agladioglu SY;Dilek SO;Evliyaoglu O;Darendeliler F;Gurbuz F;Akkus G;Yuksel B;Giacobini P;Topaloglu AK
通讯作者：
Topaloglu AK