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

Weilai Dong, Clinton Baldwin, Jungmin Choi, Jeff M. Milunsky, Junhui Zhang, Kaya Bilguvar, Richard P. Lifton, Aubrey Milunsky

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)473-477
Number of pages5
JournalClinical Genetics
Volume96
Issue number5
DOIs
Publication statusPublished - 2019 Nov 1
Externally publishedYes

Keywords

  • Chronic Intestinal Pseudo-Obstruction
  • exome-sequencing
  • genetics
  • MYH11

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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