caa a22 4500 445861029 CHVBK 20180317145443.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00439-011-1006-9 doi (NATIONALLICENCE)springer-10.1007/s00439-011-1006-9 Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8 [Elektronische Daten] [Hiroshi Kaneko, Hiroshi Kitoh, Tohru Matsuura, Akio Masuda, Mikako Ito, Monica Mottes, Frank Rauch, Naoki Ishiguro, Kinji Ohno] Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in COL1A1 or COL1A2. We identified a dominant missense mutation, c.3235G>A in COL1A1 exon 45 predicting p.G1079S, in a Japanese family with mild OI. As mutations in exon 45 exhibit mild to lethal phenotypes, we tested if disruption of an exonic splicing cis-element determines the clinical phenotype, but detected no such mutations. In the Japanese family, juvenile-onset hyperuricemia cosegregated with OI, but not in the previously reported Italian and Canadian families with c.3235G>A. After confirming lack of a founder haplotype in three families, we analyzed PRPSAP1 and PRPSAP2 as candidate genes for hyperuricemia on chr 17 where COL1A1 is located, but found no mutation. We next resequenced the whole exomes of two siblings in the Japanese family and identified variable numbers of previously reported hyperuricemia-associated SNPs in ABCG2 and SLC22A12. The same SNPs, however, were also detected in normouricemic individuals in three families. We then identified two missense SNVs in ZPBP2 and GPATCH8 on chromosome 17 that cosegregated with hyperuricemia in the Japanese family. ZPBP2 p.T69I was at the non-conserved region and was predicted to be benign by in silico analysis, whereas GPATCH8 p.A979P was at a highly conserved region and was predicted to be deleterious, which made p.A979P a conceivable candidate for juvenile-onset hyperuricemia. GPATCH8 is only 5.8 Mbp distant from COL1A1 and encodes a protein harboring an RNA-processing domain and a zinc finger domain, but the molecular functions have not been elucidated to date. Springer-Verlag, 2011 Kaneko Hiroshi Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut Kitoh Hiroshi Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan aut Matsuura Tohru Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut Masuda Akio Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut Ito Mikako Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut Mottes Monica Department of Life and Reproduction Sciences, University of Verona, Verona, Italy aut Rauch Frank Genetics Unit, Shriners Hospital for Children and McGill University, Montreal, QC, Canada aut Ishiguro Naoki Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan aut Ohno Kinji Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut Human Genetics Springer-Verlag 130/5(2011-11-01), 671-683 0340-6717 130:5<671 2011 130 439 https://doi.org/10.1007/s00439-011-1006-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-1006-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kaneko Hiroshi Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut NATIONALLICENCE 700 1- Kitoh Hiroshi Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan aut NATIONALLICENCE 700 1- Matsuura Tohru Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut NATIONALLICENCE 700 1- Masuda Akio Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut NATIONALLICENCE 700 1- Ito Mikako Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut NATIONALLICENCE 700 1- Mottes Monica Department of Life and Reproduction Sciences, University of Verona, Verona, Italy aut NATIONALLICENCE 700 1- Rauch Frank Genetics Unit, Shriners Hospital for Children and McGill University, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Ishiguro Naoki Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan aut NATIONALLICENCE 700 1- Ohno Kinji Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, 466-8550, Nagoya, Japan aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/5(2011-11-01), 671-683 0340-6717 130:5<671 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer