title: Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy.
abstract: By using whole-exome sequencing, we identified a homozygous guanine-to-adenine transition at the invariant -1 position of the acceptor site of intron 1 (c.97-1G>A) in solute carrier organic anion transporter family member 2A1 (SLCO2A1), which encodes a prostaglandin transporter protein, as the causative mutation in a single individual with primary hypertrophic osteoarthropathy (PHO) from a consanguineous family. In two other affected individuals with PHO from two unrelated nonconsanguineous families, we identified two different compound heterozygous mutations by using Sanger sequencing. These findings confirm that SLCO2A1 mutations inactivate prostaglandin E(2) (PGE(2)) transport, and they indicate that mutations in SLCO2A1 are the pathogenic cause of PHO. Moreover, this study might also help to explain the cause of secondary hypertrophic osteoarthropathy.
authors.affiliation: Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University, China. zhangzhenlin2011@gmail.com
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
authors.forename: Jinwei
authors.initials: J
authors.lastname: He
authors.forename: Zeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Ke
authors.forename: Hua
authors.initials: H
authors.lastname: Yue
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Jiemei
authors.initials: J
authors.lastname: Gu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Hu
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Fu
authors.forename: Yunqiu
authors.initials: Y
authors.lastname: Hu
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D015232:Dinoprostone / Q000378:metabolism; D059472:Exome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D027361:Organic Anion Transporters / Q000235:genetics*; D010004:Osteoarthropathy, Primary Hypertrophic / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: D027361:Organic Anion Transporters; C503526:SLCO2A1 protein, human; D015232:Dinoprostone