{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:05:07Z","timestamp":1784199907615,"version":"3.55.0"},"reference-count":17,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,6,10]]},"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Brachyolmia is a heterogeneous group of skeletal dysplasias that primarily affects the spine. Clinical and genetic heterogeneity have been reported; at least three types of brachyolmia are known. <jats:italic>TRPV4<\/jats:italic> mutations have been identified in an autosomal dominant form of brachyolmia; however, disease genes for autosomal recessive (AR) forms remain totally unknown. We conducted a study on a Turkish family with an AR brachyolmia, with the aim of identifying a disease gene for AR brachyolmia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We examined three affected individuals of the family using exon capture followed by next generation sequencing and identified its disease gene, <jats:italic>PAPSS2<\/jats:italic> (phosphoadenosine-phosphosulfate synthetase 2). The patients had a homozygous loss of function mutation, c.337_338insG (p.A113GfsX18). We further examined three patients with similar brachyolmia phenotypes (two Japanese and a Korean) and also identified loss of function mutations in <jats:italic>PAPSS2<\/jats:italic>; one patient was homozygous for IVS3+2delT, and the other two were compound heterozygotes for c.616-634del19 (p.V206SfsX9) and c.1309-1310delAG (p.R437GfsX19), and c.480_481insCGTA (p.K161RfsX6) and c.661delA (p.I221SfsX40), respectively. The six patients had short-trunk short stature that became conspicuous during childhood with normal intelligence and facies. Their radiographic features included rectangular vertebral bodies with irregular endplates and narrow intervertebral discs, precocious calcification of rib cartilages, short femoral neck, and mildly shortened metacarpals. Spinal changes were very similar among the six patients; however, epiphyseal and metaphyseal changes of the tubular bones were variable.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We identified <jats:italic>PAPSS2<\/jats:italic> as the disease gene for an AR brachyolmia. <jats:italic>PAPSS2<\/jats:italic> mutations have produced a skeletal dysplasia family, with a gradation of phenotypes ranging from brachyolmia to spondylo-epi-metaphyseal dysplasia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101039","type":"journal-article","created":{"date-parts":[[2012,7,11]],"date-time":"2012-07-11T23:51:40Z","timestamp":1342050700000},"page":"533-538","source":"Crossref","is-referenced-by-count":49,"title":["<i>PAPSS2<\/i> mutations cause autosomal recessive brachyolmia"],"prefix":"10.1136","volume":"49","author":[{"given":"Noriko","family":"Miyake","sequence":"first","affiliation":[{"name":"1Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nursel H","family":"Elcioglu","sequence":"additional","affiliation":[{"name":"2Department of Pediatric Genetics, Marmara University Pendik Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aritoshi","family":"Iida","sequence":"additional","affiliation":[{"name":"3Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Isguven","sequence":"additional","affiliation":[{"name":"4Department of Pediatrics and Pediatric Endocrinology, Medeniyet University Goztepe Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Dai","sequence":"additional","affiliation":[{"name":"3Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Murakami","sequence":"additional","affiliation":[{"name":"5Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Takamura","sequence":"additional","affiliation":[{"name":"6Department of Orthopaedic Surgery, Fukuoka Children's Hospital, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Joon","family":"Cho","sequence":"additional","affiliation":[{"name":"7Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok-Hwa","family":"Kim","sequence":"additional","affiliation":[{"name":"8Department of Radiology, Ajou University Hospital, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonobu","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"9Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Nagai","sequence":"additional","affiliation":[{"name":"5Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Ohashi","sequence":"additional","affiliation":[{"name":"10Division of Medical Genetics, Saitama Children's Medical Center, Saitama, 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