Mutations in PYCR1 cause cutis laxa with progeroid features

Bruno Reversade; Nathalie Escande-Beillard; Aikaterini Dimopoulou; Bjoern Fischer; Serene C. Chng; Yun Li; Mohammad Shboul; Puay-Yoke Tham; Huelya Kayserili; Lihadh Al-Gazali; Monzer Shahwan; Francesco Brancati; Hane Lee; Brian D. O'Connor; Mareen Schmidt-von Kegler; Barry Merriman; Stanley F. Nelson; Amira Masri; Fawaz Alkazaleh; Deanna Guerra; Paola Ferrari; Arti Nanda; Anna Rajab; David Markie; Mary Gray; John Nelson; Arthur Grix; Annemarie Sommer; Ravi Savarirayan; Andreas R. Janecke; Elisabeth Steichen; David Sillence; Ingrid Hausser; Birgit Budde; Gudrun Nuernberg; Peter Nuernberg; Petra Seemann; Desiree Kunkel; Giovanna Zambruno; Bruno Dallapiccola; Markus Schuelke; Stephen Robertson; Hanan Hamamy; Bernd Wollnik; Lionel Van Maldergem; Stefan Mundlos; Uwe Kornak

doi:10.1038/ng.413

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Mutations in PYCR1 cause cutis laxa with progeroid features

Journal article

Peer reviewed

Mutations in PYCR1 cause cutis laxa with progeroid features

Bruno Reversade, Nathalie Escande-Beillard, Aikaterini Dimopoulou, Bjoern Fischer, Serene C. Chng, Yun Li, Mohammad Shboul, Puay-Yoke Tham, Huelya Kayserili, Lihadh Al-Gazali, …

Nature genetics, Vol.41(9), pp.1016-U88

01/09/2009

DOI: https://doi.org/10.1038/ng.413

PMID: 19648921

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation(1-3). Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high- throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues.

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Title: Mutations in PYCR1 cause cutis laxa with progeroid features
Creators - without role: Bruno Reversade - Institute of Medical Biology
Nathalie Escande-Beillard - Institute of Medical Biology
Aikaterini Dimopoulou - Charité - Universitätsmedizin Berlin
Bjoern Fischer - Charité - Universitätsmedizin Berlin
Serene C. Chng - Institute of Medical Biology
Yun Li - University of Cologne
Mohammad Shboul - Institute of Medical Biology
Puay-Yoke Tham - Institute of Medical Biology
Huelya Kayserili - Istanbul University
Lihadh Al-Gazali - United Arab Emirates University
Monzer Shahwan - Natl Ctr Diabet Endocrinol & Genet, Amman, Jordan
Francesco Brancati - University of Chieti-Pescara
Hane Lee - University of California, Los Angeles
Brian D. O'Connor - Supreme Council Of Health
Mareen Schmidt-von Kegler - Charité - Universitätsmedizin Berlin
Barry Merriman - University of California, Los Angeles
Stanley F. Nelson - University of California, Los Angeles
Amira Masri - University of Jordan
Fawaz Alkazaleh - University of Jordan
Deanna Guerra - University of Modena and Reggio Emilia
Paola Ferrari - University of Modena and Reggio Emilia
Arti Nanda - Al-Sabah Hospital
Anna Rajab - Ministry of Health
David Markie - University of Otago
Mary Gray - University of Otago
John Nelson - King Edward Memorial Hospital
Arthur Grix - Colorado Permanente Medical Group
Annemarie Sommer - Nationwide Children's Hospital
Ravi Savarirayan - Victorian Clinical Genetics Services
Andreas R. Janecke - Innsbruck Medical University
Elisabeth Steichen - Univ Innsbruck, Klin Kinder & Jugendheilkunde, A-6020 Innsbruck, Austria
David Sillence - Children's Hospital at Westmead
Ingrid Hausser - Hautklinik Heidelberg
Birgit Budde - University of Cologne
Gudrun Nuernberg - University of Cologne
Peter Nuernberg - University of Cologne
Petra Seemann - Max Planck Institute for Molecular Genetics
Desiree Kunkel - Charité - Universitätsmedizin Berlin
Giovanna Zambruno - Istituto Dermopatico dell'Immacolata
Bruno Dallapiccola - Casa Sollievo della Sofferenza
Markus Schuelke - Charité - Universitätsmedizin Berlin
Stephen Robertson - University of Otago
Hanan Hamamy - Natl Ctr Diabet Endocrinol & Genet, Amman, Jordan
Bernd Wollnik - Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
Lionel Van Maldergem - Centre Hospitalier Universitaire de Liège
Stefan Mundlos - Charité - Universitätsmedizin Berlin
Uwe Kornak - Charité - Universitätsmedizin Berlin
Publication Details: Nature genetics, Vol.41(9), pp.1016-U88
Publisher: Springer Nature
Number of pages: 8
Grant note: 01GM0623 / German Federal Ministry of Education and Research ( BMBF); Federal Ministry of Education & Research (BMBF) 01GM0880; 01GM0801 / Deutsche Forschungsgemeinschaft; German Research Foundation (DFG)
Identifiers: 9945759908331
Academic Unit: King Abdullah University of Science & Technology
Language: English
Resource Type: Journal article