Aberrant transcription of the LHCGR gene caused by a mutation in exon 6A leads to Leydig cell hypoplasia type II
Aberrant transcription of the LHCGR gene caused by a mutation in exon 6A leads to Leydig cell hypoplasia type II
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DOI：
10.1016/j.mce.2012.11.018
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发表时间：
2013-02-05
影响因子：
4.1
通讯作者：
Gromoll, Joerg
中科院分区：
文献类型：
--
作者：
Kossack, Nina;Troppmann, Britta;Gromoll, Joerg
黄体生成素/绒毛膜促性腺激素受体（LHCGR）对正常男性性别分化至关重要。最近，LHCGR的另一个灵长类特异性外显子6A被发现，并被证明在转录水平上起调控元件的作用。外显子6A的复合杂合突变（c.580）在46，XY男性生殖器畸形患者的LHCGR中发现了一个> G)和11外显子（C . 1244t > C）。分析表明，外显子6A的c.580A > G突变影响剪接模式，导致含有外显子6A内部变异体的转录本增加，容易发生无义介导的衰变。相比之下，突变C . 1244t > C导致氨基酸取代（Ile415Thr），由于结构改变而取消信号转导。当以复合杂合方式遗传时，这些突变导致间质细胞发育不全（LCH） II型。因此，本研究证明了引起异常转录的突变可以损害受体功能，从而导致LCH。2012爱思唯尔爱尔兰有限公司版权所有。
The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for normal male sex differentiation. Recently, the additional primate-specific exon 6A of the LHCGR was discovered and it was shown to act as regulatory element at the transcriptional level.Compound heterozygous mutations in exon 6A (c.580 A > G) and exon 11 (c.1244T > C) were identified in the LHCGR of a male 46,XY patient with genital malformation. Analysis revealed that mutation c.580A > G in exon 6A affects the splicing pattern resulting in an increase of transcripts containing the internal variants of exon 6A prone to nonsense-mediated decay. In contrast, mutation c.1244T > C results in an amino acid substitution (Ile415Thr), which abolishes signal transduction due to structural changes. When inherited in a compound heterozygous fashion these mutations result in Leydig cell hypoplasia (LCH) type II. Thus this study provides proof that mutations causing aberrant transcription can impair receptor function and thereby be causative of LCH. (C) 2012 Elsevier Ireland Ltd. All rights reserved.