Gastrointestinal Dysmotility Is a Significant Feature in 2 Siblings With a Novel Inositol 1,4,5-Triphosphate Receptor 1 () Missense Variant.

We present 2 siblings with a novel type 1 inositol 1,4,5-triphosphate receptor () missense variant who exhibit gastrointestinal dysmotility (chronic constipation and gastroparesis). is expressed in the cerebellum and interstitial cells of Cajal. Periodic release of calcium by initiates pacemaker currents, resulting in smooth muscle contraction. mutations are known to be associated with neurologic syndromes, and these variants have not previously been associated with significant gastrointestinal manifestations in humans. Using whole-genome sequencing, prediction software, biopsy samples, and manometry, the identified novel variant is likely pathogenic and may have neurogastroenterology implications.