一个中国复发性流产家系中两个新的 TMEM67 变异：病例报告。
Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report.
机构信息
Department of Medical Genetics, Maternal and Child Health Hospital of Hunan Province, 58 Xiangchun Road, Changsha, 410078, Hunan, China.
Medical Record Management Department, Maternal and Child Health Hospital of Hunan Province, Changsha, Hunan, China.
出版信息
BMC Med Genomics. 2024 Jun 6;17(1):156. doi: 10.1186/s12920-024-01902-x.
BACKGROUND
Recurrent pregnancy loss (RPL) is a common pregnancy complication that brings great pain to pregnant women and their families. Genetic factors are an important cause reason of RPL. However, clinical research on monogenic diseases with recurrent miscarriage is insufficient.
CASE PRESENTATION
Here we reported a Chinese family with RPL and genetic analysis of the abortion and parents. A paternally inherited heterozygous missense variant c.1415T > G (p.V472G) and a maternally inherited heterozygous nonsense variant c.2314del (p.M772*) in TMEM67 gene were identified by trio-exome sequencing. c.2314del (p.M772*) generated a premature stop codon and truncated protein, was classified as "pathogenic". c.1415T > G (p.V472G) located in extra-cellular region, was classified as "likely pathogenic". Biallelic variants in TMEM67 gene cause lethal Meckel syndrome 3, consistent with the proband's prenatal phenotype.
CONCLUSION
The current study of the Chinese family expands the pathogenic variant spectrum of TMEM67 and emphasizes the necessity of exome sequencing in RPL condition.
背景
复发性妊娠丢失（RPL）是一种常见的妊娠并发症，给孕妇及其家庭带来了巨大的痛苦。遗传因素是 RPL 的一个重要原因。然而，临床上对复发性流产的单基因疾病的研究还不够充分。
病例介绍
我们在这里报告了一个 RPL 中国家庭，并对流产和父母进行了基因分析。通过三核苷酸外显子组测序，发现 TMEM67 基因的一个父系遗传杂合错义变异 c.1415T>G(p.V472G)和一个母系遗传杂合无义变异 c.2314del(p.M772*)。c.2314del(p.M772*)产生了一个提前终止密码子并截断了蛋白，被归类为“致病性”。c.1415T>G(p.V472G)位于细胞外区，被归类为“可能致病性”。TMEM67 基因的双等位基因变异导致致死性 Meckel 综合征 3，与先证者的产前表型一致。
结论
本研究扩展了 TMEM67 的致病变异谱，并强调了外显子组测序在 RPL 情况下的必要性。
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