Mutations in the Human UBR1 Gene and the Associated Phenotypic Spectrum

Mutations in the Human UBR1 Gene and the Associated Phenotypic Spectrum

Author Sukalo, Maja Google Scholar
Fiedler, Ariane Google Scholar
Guzman, Celina Google Scholar
Spranger, Stephanie Google Scholar
Addor, Marie-Claude Google Scholar
Mcheik, Jiad N. Google Scholar
Benavent, Manuel Oltra Google Scholar
Cobben, Jan M. Google Scholar
Gillis, Lynette A. Google Scholar
Shealy, Amy G. Google Scholar
Deshpande, Charu Google Scholar
Bozorgmehr, Bita Google Scholar
Everman, David B. Google Scholar
Stattin, Eva-Lena Google Scholar
Liebelt, Jan Google Scholar
Keller, Klaus-Michael Google Scholar
Bertola, Debora Romeo Google Scholar
van Karnebeek, Clara D. M. Google Scholar
Bergmann, Carsten Google Scholar
Liu, Zhifeng Google Scholar
Dueker, Gesche Google Scholar
Rezaei, Nima Google Scholar
Alkuraya, Fowzan S. Google Scholar
Ogur, Gonul Google Scholar
Alrajoudi, Abdullah Google Scholar
Venegas-Vega, Carlos A. Google Scholar
Verbeek, Nienke E. Google Scholar
Richmond, Erick J. Google Scholar
Kirbiyik, Ozgur Google Scholar
Ranganath, Prajnya Google Scholar
Singh, Ankur Google Scholar
Godbole, Koumudi Google Scholar
Ali, Fouad A. M. Google Scholar
Alves, Cresio Google Scholar
Mayerle, Julia Google Scholar
Lerch, Markus M. Google Scholar
Witt, Heiko Google Scholar
Zenker, Martin Google Scholar
Institution Univ Hosp Magdeburg
Univ Hosp Erlangen
Hosp Nacl Ninos Dr Carlos Saenz Herrera
Klinikum Bremen Mitte
CHU Vaudois
Univ Hosp
Hosp La Fe
AMC Univ Hosp
Vanderbilt Univ
Cleveland Clin
Guys Hosp
Kariminejad Najmabadi Pathol & Genet Ctr
Greenwood Genet Ctr
Umea Univ
Womens & Childrens Hosp
Stiftung Deutsch Klin Diagnost GmbH
Universidade Federal de São Paulo (UNIFESP)
Univ British Columbia
Ctr Human Genet
Nanjing Med Univ
Univ Klinikum Bonn
Univ Tehran Med Sci
King Faisal Specialist Hosp & Res Ctr
Ondokuz Mayis Univ
Al Thawra Teaching Hosp
Hosp Gen Mexico City
Univ Med Ctr Utrecht
Natl Childrens Hosp
Sisli Etfal Res Hosp
Nizams Inst Med Sci
Maulana Azad Med Coll
Deenanath Mangeshkar Hosp & Res Ctr
Minist Hlth
Universidade Federal da Bahia (UFBA)
Ernst Moritz Arndt Univ Greifswald
Tech Univ Munich
Abstract Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n=29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. the review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. for all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.
Keywords Johanson-Blizzard syndrome
exocrine pancreatic insufficiency
aplasia of alae nasi
cognitive impairment
Language English
Sponsor German Research Foundation
Grant number German Research Foundation: DFG ZE 524/2-3
Date 2014-05-01
Published in Human Mutation. Hoboken: Wiley-Blackwell, v. 35, n. 5, p. 521-531, 2014.
ISSN 1059-7794 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 521-531
Access rights Closed access
Type Article
Web of Science ID WOS:000334658800003

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