title: Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia.
abstract: Opsismodysplasia is an autosomal recessive skeletal disorder characterized by facial dysmorphism, micromelia, platyspondyly and retarded bone maturation. Recently, mutations in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1) are found in several families with opsismodysplasia by a homozygosity mapping, followed by whole genome sequencing. We performed an exome sequencing in two unrelated Japanese families with opsismodysplasia and identified a novel INPPL1 mutation, c.1960_1962delGAG, in one family. The mutation is predicted to result in an in-frame deletion (p.E654del) within the central catalytic 5-phosphate domain. Our results further support that INPPL1 is the disease gene for opsismodysplasia and that opsismodysplasia has genetic heterogeneity.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minami
authors.forename: Takuya
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogata
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002648:Child; D059472:Exome; D005260:Female; D017353:Gene Deletion; D018740:Genetic Heterogeneity; D006720:Homozygote; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases