{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:27:28Z","timestamp":1761514048638,"version":"3.37.3"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T00:00:00Z","timestamp":1501459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003390","name":"Fritz Thyssen Stiftung","doi-asserted-by":"publisher","award":["AZ 10.15.2.040MN"],"award-info":[{"award-number":["AZ 10.15.2.040MN"]}],"id":[{"id":"10.13039\/501100003390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2017,11]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Johanson\u2010Blizzard syndrome (JBS<\/jats:styled-content>,MIM<\/jats:styled-content>#243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities.JBS<\/jats:styled-content>is caused by mutations of theUBR<\/jats:styled-content>1<\/jats:italic>gene (MIM<\/jats:styled-content>*605981), encoding a ubiquitin ligase of the N\u2010end rule pathway.<\/jats:p><\/jats:sec>Methods<\/jats:title>Molecular findings in a total of 65 unrelated patients with a clinical diagnosis ofJBS<\/jats:styled-content>who were previously screened forUBR<\/jats:styled-content>1 mutations by Sanger sequencing were reviewed and cases lacking a disease\u2010causingUBR<\/jats:styled-content>1 mutation on either one or both alleles were included in this study. In order to discover mutations that are not detectable by Sanger sequencing, we designed a probe set for multiplex ligation\u2010dependent probe amplification (MLPA<\/jats:styled-content>) analysis of theUBR<\/jats:styled-content>1<\/jats:italic>gene and analyzed the copy number status of all 47UBR<\/jats:styled-content>1<\/jats:italic>exons.<\/jats:p><\/jats:sec>Results<\/jats:title>Our previous studies using Sanger sequencing could detect mutations in 93.1% of 130 disease\u2010associatedUBR<\/jats:styled-content>1<\/jats:italic>alleles. Six patients with a highly suggestive clinical diagnosis ofJBS<\/jats:styled-content>and unsolved genotype were included in this study.MLPA<\/jats:styled-content>analysis detected six alleles harboring exon deletions\/duplications, thereby raising the mutation detection rate in the entire cohort to 97.7% (127\/130 alleles).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>We conclude that single or multi\u2010exon deletions or duplications account for a substantial proportion ofJBS<\/jats:styled-content>\u2010associatedUBR<\/jats:styled-content>1<\/jats:italic>mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.319","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T04:02:49Z","timestamp":1501560169000},"page":"774-780","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Expanding the mutational spectrum in Johanson\u2010Blizzard syndrome: identification of whole exon deletions and duplications in theUBR<\/scp>1<\/i>gene by multiplex ligation\u2010dependent probe amplification analysis"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2269-1063","authenticated-orcid":false,"given":"Maja","family":"Sukalo","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Sch\u00e4flein","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Erlangen\u2010Nuremberg Erlangen Germany"},{"name":"Department of Psychosomatic Medicine and Psychotherapy University Hospital Rechts der Isar, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Schanze","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Everman","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood South Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nima","family":"Rezaei","sequence":"additional","affiliation":[{"name":"Research Center for Immunodeficiencies Children's Medical Center Tehran University of Medical Sciences Tehran Iran"},{"name":"Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA) Universal Scientific Education and Research Network (USERN) Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Argente","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology and Pediatrics and Instituto de Investigaci\u00f3n La Princesa Hospital Infantil Universitario Ni\u00f1o Jes\u00fas Madrid Spain"},{"name":"Department of Pediatrics Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN) Instituto de Salud Carlos III Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Lorda\u2010Sanchez","sequence":"additional","affiliation":[{"name":"Department of Genetics IIS\u2010Fundaci\u00f3n Jim\u00e9nez D\u00edaz UAM CIBERER Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charu","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Clinical Genetics Guy's Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Akita University Graduate School of Medicine Akita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Kleger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Medical Center Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Zenker","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(71)80194-4"},{"volume-title":"GeneReviews\u00ae [Internet]","author":"Pagon R. 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Doctoral Dissertation Magdeburg: Universit\u00e4tsbibliothek (urn:nbn:de:gbv:ma9:1\u20108497).https:\/\/doi.org\/10.13140\/rg.2.2.14992.61446."},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22538"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.2004.17.8.1141"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.22.12142"},{"key":"e_1_2_3_10_1","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1093\/oso\/9780195306910.003.0135","volume-title":"Inborn errors of development","author":"Zenker M.","year":"2008"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1681"}],"container-title":["Molecular Genetics & Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.319","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T22:11:56Z","timestamp":1719353516000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,31]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1002\/mgg3.319"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.319","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2017,7,31]]},"assertion":[{"value":"2017-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}