We present 2 siblings with a novel type 1 inositol 1,4,5-triphosphate receptor (ITPR1) missense variant who exhibit gastrointestinal dysmotility (chronic constipation and gastroparesis). ITPR1 is expressed in the cerebellum and interstitial cells of Cajal. Periodic release of calcium by ITPR1 initiates pacemaker currents, resulting in smooth muscle contraction. ITPR1 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, in silico prediction software, biopsy samples, and manometry, the identified novel ITPR1 variant is likely pathogenic and may have neurogastroenterology implications.
© 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.