Autosomal Recessive ACTG2-Related Visceral Myopathy in Brothers.

Autor: Mori M; From the Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH.; Department of Pediatrics, The Ohio State University, Columbus, OH., Clause AR; Illumina Inc., San Diego, CA., Truxal K; From the Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH.; Department of Pediatrics, The Ohio State University, Columbus, OH., Hagelstrom RT; Illumina Inc., San Diego, CA., Manickam K; From the Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH.; Department of Pediatrics, The Ohio State University, Columbus, OH., Kaler SG; From the Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH.; Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH., Prasad V; Department of Pediatrics, The Ohio State University, Columbus, OH.; Pathology & Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH., Windster J; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.; Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands., Alves MM; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Di Lorenzo C; Department of Pediatrics, The Ohio State University, Columbus, OH.; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital, Columbus, OH.
Jazyk: angličtina
Zdroj: JPGN reports [JPGN Rep] 2022 Oct 20; Vol. 3 (4), pp. e258. Date of Electronic Publication: 2022 Oct 20 (Print Publication: 2022).
DOI: 10.1097/PG9.0000000000000258
Abstrakt: Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous condition characterized by impaired gastrointestinal propulsion, a broad clinical spectrum, and variable severity. Several molecular bases underlying primary PIPO have been identified, of which autosomal dominant ACTG2-related visceral myopathy is the most common in both familial or sporadic primary PIPO cases. We present a family with autosomal recessive ACTG2-related disease in which both parents have mild gastrointestinal symptoms and sons have severe PIPO and bladder dysfunction.
Methods: Clinical genome sequencing was performed on the patients and the mother. Immunohistochemistry was performed on intestinal tissue from the patients to show expression levels of the ACTG2 .
Results: Genome sequencing identified a 6.8 kb 2p13.1 loss that includes the ACTG2 gene and a maternally inherited missense variant p.Val10Met in the ACTG2 gene.
Discussion: This case demonstrates that monoallelic hypomorphic ACTG2 variants may underly mild primary gastrointestinal symptoms, while biallelic mild variants can cause severe diseases. The Deletions of the noncoding ACTG2 exon can be an under-recognized cause of mild gastrointestinal symptoms unidentifiable by exome sequencing, explaining some instances of interfamilial variability with an apparent autosomal dominant inheritance. Genome sequencing is recommended as a genetic work-up for primary or idiopathic PIPO because of genetic heterogeneity.
Competing Interests: Dr Di Lorenzo receives consultant fees from Sucampo, Allergan, QOL Inc, Mahana, Innovative Health Solutions, and Mallinckrodt. Dr Kaler receives Consultant fees from Vivet Therapeutics, Inc. (Paris, France) as chair of a clinical trial Data Monitoring Committee. AC is an employee and shareholder of Illumina, Inc. The remaining authors report no conflicts of interest.
(Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
Databáze: MEDLINE
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