Heterozygous and Inherited Mutations in the Smooth Muscle Actin () Gene Underlie Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome

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In 1976, a radiologist, Walter Berdon described a group of patients with a rare intestinal and bladder disorder in which the smooth muscle of those organs failed to contract. These patients are unable to digest food, require multiple abdominal surgeries and are diagnosed with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). Since the description of MMIHS, the genes that cause it have remained a mystery. We followed and obtained DNA from patients with this disorder over a period of over 14 years and assembled a large group of cases. We used whole-exome sequencing, a powerful tool used to identify disease genes, and found mutations in ACTG2, a visceral actin gene. Actins are components of muscle contractile units, and one Finnish family has been previously found with less severe gastrointestinal problems due to mutations in this gene. In our patients, we find de novo mutations in the majority of cases of MMIHS. However, we also find families with the disease over several generations due to these same mutations. This work provides the first disease gene for MMIHS, and suggests new treatment options.

Vyšlo v časopise: Heterozygous and Inherited Mutations in the Smooth Muscle Actin () Gene Underlie Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004258
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004258

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