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在一个复发性羊水过少的家族中鉴定出血管紧张素转换酶基因的两个新的致病性变异。

Two novel deleterious variants of Angiotensin-I-converting Enzyme gene identified in a family with recurrent anhydramnios.

机构信息

Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

Department of obstetrics, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Mol Genet Genomic Med. 2020 Jun;8(6):e1239. doi: 10.1002/mgg3.1239. Epub 2020 Apr 23.

DOI:10.1002/mgg3.1239
PMID:32329243
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7284050/
Abstract

BACKGROUND

Anhydramnios results from the poor development of the placenta or problems with intrauterine development of the kidneys or urinary tract. Complete lack of amniotic fluid indicates a severe problem with the organs of the urinary system. The genes associated with anhydramnios show very diversity and are not yet well defined.

METHODS

Whole-exome sequencing (WES) was used for an aborted male case around the 20th week of gestation diagnosed with anhydramnios. The resulted deleterious variants were verified by Sanger sequencing. Pathogenicity of deleterious variants was explored by in silico analysis.

RESULTS

A maternally inherited deleterious frameshift variant, c.1454_1455insC, p.(S486Ffs29) in exon 9 and two paternally inherited missense variants c.1037C > G, p.(Ser346Trp) in exon 7 and c.1465A > G, p.(Asn489Asp) in exon 9 of Angiotensin-I-Converting Enzyme (ACE) gene were found and confirmed by Sanger sequencing. c.1454_1455insC, p.(S486Ffs29) and c.1037C > G, p.(Ser346Trp) were identified as two novel compound heterozygous deleterious variants. The pathogenicity of these deleterious variants was determined by in silico analysis and both the deleterious variants disrupt the structure of the ACE protein.

CONCLUSION

Two novel compound heterozygous variants were identified in the case with anhydramnios, which may be associated with pathogenicity of anhydramnios. Our data also revealed that the WES approach may provide helpful information for genetic counseling of the families with anhydramnios.

摘要

背景

羊水过少是由于胎盘发育不良或胎儿肾脏或泌尿道宫内发育问题引起的。完全没有羊水表明泌尿系统器官严重问题。与羊水过少相关的基因表现出非常多样性，尚未得到很好的定义。

方法

对一名 20 孕周左右被诊断为羊水过少的男性流产胎儿进行全外显子组测序（WES）。通过 Sanger 测序验证所得的有害变异。通过计算机分析探索有害变异的致病性。

结果

发现一个母系遗传的有害移码变异 c.1454_1455insC，p.（S486Ffs29），位于 9 号外显子，以及两个父系遗传的错义变异 c.1037C>G，p.（Ser346Trp），位于 7 号外显子和 c.1465A>G，p.（Asn489Asp），位于 9 号外显子的血管紧张素转换酶（ACE）基因。通过 Sanger 测序证实了 c.1454_1455insC，p.（S486Ffs29）和 c.1037C>G，p.（Ser346Trp）为两个新的复合杂合有害变异。通过计算机分析确定了这些有害变异的致病性，这两种有害变异都破坏了 ACE 蛋白的结构。

结论

在羊水过少的病例中发现了两个新的复合杂合变异，这可能与羊水过少的发病机制有关。我们的数据还表明，WES 方法可以为羊水过少患者的遗传咨询提供有帮助的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/0e6f0abdf1dd/MGG3-8-e1239-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/a4d4ba17b7b5/MGG3-8-e1239-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/9cefb1613b86/MGG3-8-e1239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/7d2a0280b30e/MGG3-8-e1239-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/79e79da5cc3c/MGG3-8-e1239-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/0e6f0abdf1dd/MGG3-8-e1239-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/a4d4ba17b7b5/MGG3-8-e1239-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/9cefb1613b86/MGG3-8-e1239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/7d2a0280b30e/MGG3-8-e1239-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/79e79da5cc3c/MGG3-8-e1239-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77a3/7284050/0e6f0abdf1dd/MGG3-8-e1239-g005.jpg

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