1. Academic Validation
  2. Identification of a dominant MYH11 causal variant in chronic intestinal pseudo-obstruction: Results of whole-exome sequencing

Identification of a dominant MYH11 causal variant in chronic intestinal pseudo-obstruction: Results of whole-exome sequencing

  • Clin Genet. 2019 Nov;96(5):473-477. doi: 10.1111/cge.13617.
Weilai Dong 1 Clinton Baldwin 2 Jungmin Choi 1 3 Jeff M Milunsky 2 Junhui Zhang 1 Kaya Bilguvar 1 Richard P Lifton 3 Aubrey Milunsky 2
Affiliations

Affiliations

  • 1 Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.
  • 2 Center for Human Genetics and Dept. Ob/Gyn, Tufts University School of Medicine, Boston, Massachusetts.
  • 3 Laboratory of Human Genetics and Genomics, Rockefeller University, New York, New York.
Abstract

Chronic Intestinal Pseudo-Obstruction (CIPO) is a rare gastrointestinal disorder, which affects the smooth muscle contractions of the gastrointestinal tract. Dominant mutations in the smooth muscle actin gene, ACTG2, accounts for 44%-50% of CIPO patients. Other recessive or X-linked genes, including MYLK, LMOD1, RAD21, MYH11, MYL9, and FLNA were reported in single cases. In this study, we used Whole-Exome Sequencing (WES) to study 23 independent CIPO families including one extended family with 13 affected members. A dominantly inherited rare mutation, c.5819delC (p.Pro1940HisfsTer91), in the smooth muscle Myosin gene, MYH11, was found in the extended family, shared by 7 affected family members but not by 3 unaffected family members with available DNA, suggesting a high probability of genetic linkage. Gene burden analysis indicates that additional genes, COL4A1, FBLN1 and HK2, may be associated with the disease. This study expanded our understanding of CIPO etiology and provided additional genetic evidence to physicians and genetic counselors for CIPO diagnosis.

Keywords

MYH11; Chronic Intestinal Pseudo-Obstruction; exome-sequencing; genetics.

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