Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia

  • Am J Hum Genet. 2013 Jan 10;92(1):137-43. doi: 10.1016/j.ajhg.2012.11.011.
Jennifer E Below  1 ,  Dawn L Earl ,  Kathryn M Shively ,  Margaret J McMillin ,  Joshua D Smith ,  Emily H Turner ,  Mark J Stephan ,  Lihadh I Al-Gazali ,  Jozef L Hertecant ,  David Chitayat ,  Sheila Unger ,  Daniel H Cohn ,  Deborah Krakow ,  James M Swanson ,  Elaine M Faustman ,  Jay Shendure ,  Deborah A Nickerson ,  Michael J Bamshad ,  University of Washington Center for Mendelian Genomics
Affiliations
  • 1. Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
PMID: 23273567 DOI: 10.1016/j.ajhg.2012.11.011
Abstract

Opsismodysplasia is a rare, autosomal-recessive skeletal dysplasia characterized by short stature, characteristic facial features, and in some cases severe renal phosphate wasting. We used linkage analysis and whole-genome Sequencing of a consanguineous trio to discover that mutations in inositol polyphosphate phosphatase-like 1 (INPPL1) cause opsismodysplasia with or without renal phosphate wasting. Evaluation of 12 families with opsismodysplasia revealed that INPPL1 mutations explain ~60% of cases overall, including both of the families in our cohort with more than one affected child and 50% of the simplex cases.