Compound heterozygous variants in MYH11 underlie autosomal recessive megacystis-microcolon-intestinal hypoperistalsis syndrome in a Chinese family.

MYH11 中的复合杂合变异是中国家庭常染色体隐性遗传巨细胞 - 微结肠 - 肠蠕动综合征的基础。

• 影响指数: 3.755
• 发表时间: Nov 2019
• 来源期刊: J Hum Genet
• DOI: 10.1038/s10038-019-0651-z
• PMID: 31427716
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Wang Q,Zhang J,Wang H,Feng Q,Luo F,Xie J

Mesh: Abnormalities, Multiple / genetics physiopathology; Colon / abnormalities physiopathology; Female; Fetus; Gastrointestinal Tract / pathology; Genes, Recessive; Genetic Predisposition to Disease; Heterozygote; Humans; Intestinal Pseudo-Obstruction / genetics physiopathology; Male; Mutation; Myosin Heavy Chains / genetics; Phenotype; Polymorphism, Single Nucleotide / genetics; Pregnancy; Urinary Bladder / abnormalities physiopathology; Urinary Tract / pathology; Whole Exome Sequencing

Abstract

Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a rare and severe disorder characterized by functional obstruction in the urinary and gastrointestinal tract. The molecular basis of this condition has been defined recently. Heterozygous variants in ACTG2, homozygous mutations in LMOD1, MYLK, and MYH9 were related to the pathogenesis of the syndrome, which encodes proteins involved in the process of smooth muscle contraction, supporting a myopathic basis for the disease. Recent studies have identified homozygous or compound heterozygous variants in MYH11 as a candidate gene of MMIHS. In this report, we described a nonconsanguineous Chinese family with three male fetuses affected with megacystis. Trio-targeted exome sequencing identified compound heterozygous variants, c.2051 G > A (p.R684H) and c.3540_3541delinsTT (p.(E1180D, Q1181Ter)), in MYH11 (NM_001040114). The variants were inherited from the parents, respectively. Western blotting showed a marked decrease in MYH11 protein in the proband\'s umbilical cord tissue compared with the control sample. The study\'s results confirmed that MYH11 is a candidate gene for MMIHS with autosomal recessive (AR) inheritance and expanded the mutation spectrum for this clinical condition. Combining clinical phenotype with molecular diagnosis may enable the identification of candidate genes for potential monogenic diseases and facilitate accurate genetic counseling, informed decision-making, and prenatal diagnosis.