title: Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia.
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.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Below
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Earl
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Shively
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: McMillin
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.forename: Emily H
authors.initials: EH
authors.lastname: Turner
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Stephan
authors.forename: Lihadh I
authors.initials: LI
authors.lastname: Al-Gazali
authors.forename: Jozef L
authors.initials: JL
authors.lastname: Hertecant
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Cohn
authors.forename: Deborah
authors.initials: D
authors.lastname: Krakow
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Faustman
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bamshad
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D015894:Genome, Human; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*
chemical_list: D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases