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Identification of a dominant MYH11 causal variant in chronic intestinal pseudo‐obstruction: Results of whole‐exome sequencing
Author(s) -
Dong Weilai,
Baldwin Clinton,
Choi Jungmin,
Milunsky Jeff M.,
Zhang Junhui,
Bilguvar Kaya,
Lifton Richard P.,
Milunsky Aubrey
Publication year - 2019
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13617
Subject(s) - exome sequencing , identification (biology) , intestinal pseudo obstruction , genetics , biology , exome , computational biology , medicine , mutation , gene , botany
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.