Autosomal Recessive ACTG2-Related Visceral Myopathy in Brothers.

UNLABELLED

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 .

RESULTS

Genome sequencing identified a 6.8 kb 2p13.1 loss that includes the gene and a maternally inherited missense variant p.Val10Met in the gene.

DISCUSSION

This case demonstrates that monoallelic hypomorphic variants may underly mild primary gastrointestinal symptoms, while biallelic mild variants can cause severe diseases. The Deletions of the noncoding 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.