Mutations in Pycrl Cause Cutis Laxa with Progeroid Features Genetics
nature genetics Mg101 Mutations in PYCRl cause cutis laxa with progeroid features Bruno Reversade1 •33, Nathalie Escande-Beillard Aikaterini Dimopoulou2, Björn Fischer2, Serene C Chng1, Yun Li3, Mohammad Shboul1, Puay-Yoke Tham1, Hülya Kayserilf, Lihadh Al-Gazali5, Monzer Shahwan6, Francesco Brancati7'8, Hane Lee9, Brian D O'Connor9, Mareen Schmidt-von Kegler2' 10, Barry Merriman9, Stanley F Nelson9, Amira Masri11 , Fawaz Deanna Guerra12, Paola Ferrari13, Arti Nanda14, Anna Rajab 15 , David Markie16, Mary Gray16, John Nelson17, Arthur Grix18, Annemarie Sommer19, Ravi Savarirayan20, Andreas R Janecke21 , 22, 23, lal Elisabeth Steichen David Sillence Ingrid HauBer24, e Birgit Budde25, Gudrun Nürnberg25, Peter Nürnberg25, Petra Seemann10,26, Desiree Kunkel26, Giovanna Zamhruno27, Bruno Dallapiccola7, Markus Schuelke28, Stephen Robertson29, Hanan Hamamy6, Ol 32 2 10 26 ·;:: Bernd Lionel Van Maldergem , Stefan Mundlos • • & Uwe Autosomal recessive cutis laxa (ARCL) describes a group findings link mutations in PYCR1 to altered mitochondrial of syndromal disorders that are often associated with a function and progeroid changes in connective tissues. progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation 1- 3• Homozygosity mapping in Wrinkly skin and bone loss are typical features associated with several kindreds with ARCL identified a candidate region aging. In some monogenetic diseases these changes occur prema- e on chromosome 17q25. By high-throughput sequencing of turely, resulting in a progeroid appearance of affected individuals. 1ii the entire candidate region, we detected disease-causing As a clinical feature, wrinkly skin or cutis laxa is used as a z mutations in the gene PYCR1. We found that the gene common denominator of several overlapping syndromal disorders product, an enzyme involved in proline metabolism, localizes including autosomal dominant cutis laxa (MIM123700), autoso- to mitochondria.
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