{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:47:17Z","timestamp":1774950437913,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education and Scientific Research in Tunisia","award":["(LR16IPT\/05)"],"award-info":[{"award-number":["(LR16IPT\/05)"]}]},{"name":"\u201cProgrammes Transversaux de Recherche\u201d project","award":["PTR_Rejuvenage 2017-2019"],"award-info":[{"award-number":["PTR_Rejuvenage 2017-2019"]}]},{"name":"Projet Collaboratif Interne","award":["PCI_Ageing 2019_2021"],"award-info":[{"award-number":["PCI_Ageing 2019_2021"]}]},{"name":"Fellowship for PhD students","award":["MOBIDOC-753 (2017-2020)"],"award-info":[{"award-number":["MOBIDOC-753 (2017-2020)"]}]},{"name":"the Agence Nationale de la Recherche","award":["(ANR) CS_AGE"],"award-info":[{"award-number":["(ANR) CS_AGE"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cockayne syndrome (CS) is a rare disease caused by mutations in ERCC6\/CSB or ERCC8\/CSA. We report here the clinical, genetic, and functional analyses of three unrelated patients mutated in ERCC6\/CSB with a severe phenotype. After clinical examination, two patients were investigated via next generation sequencing, targeting seventeen Nucleotide Excision Repair (NER) genes. All three patients harbored a novel, c.3156dup, homozygous mutation located in exon 18 of ERCC6\/CSB that affects the C-terminal region of the protein. Sanger sequencing confirmed the mutation and the parental segregation in the three families, and Western blots showed a lack of the full-length protein. NER functional impairment was shown by reduced recovery of RNA synthesis with proficient unscheduled DNA synthesis after UV-C radiations in patient-derived fibroblasts. Despite sharing the same mutation, the clinical spectrum was heterogeneous among the three patients, and only two patients displayed clinical photosensitivity. This novel ERCC6 variant in Tunisian patients suggests a founder effect and has implications for setting-up prenatal diagnosis\/genetic counselling in North Africa, where this disease is largely undiagnosed. This study reveals one of the rare cases of CS clinical heterogeneity despite the same mutation. Moreover, the occurrence of an identical homozygous mutation, which either results in clinical photosensitivity or does not, strongly suggests that this classic CS symptom relies on multiple factors.<\/jats:p>","DOI":"10.3390\/genes12121922","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T22:50:45Z","timestamp":1638226245000},"page":"1922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification and Characterization of a Novel Recurrent ERCC6 Variant in Patients with a Severe Form of Cockayne Syndrome B"],"prefix":"10.3390","volume":"12","author":[{"given":"Khouloud","family":"Zayoud","sequence":"first","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, El Manar I, Tunis 1002, Tunisia"},{"name":"Facult\u00e9 des Sciences de Bizerte, Bizerte 7000, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichraf","family":"Kraoua","sequence":"additional","affiliation":[{"name":"LR18SP04 and Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma","family":"Chikhaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, El Manar I, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nad\u00e8ge","family":"Calmels","sequence":"additional","affiliation":[{"name":"Laboratoires de Diagnostic G\u00e9n\u00e9tique, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace, Nouvel H\u00f4pital Civil, H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"},{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, INSERM U1112, Institut de g\u00e9n\u00e9tique m\u00e9dicale d\u2019Alsace, CRBS, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami","family":"Bouchoucha","sequence":"additional","affiliation":[{"name":"Service Orthop\u00e9die, H\u00f4pital d\u2019enfant B\u00e9chir Hamza, Tunis 1000, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy","family":"Obringer","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, INSERM U1112, Institut de g\u00e9n\u00e9tique m\u00e9dicale d\u2019Alsace, CRBS, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e9ment","family":"Crochemore","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Team Stability of Nuclear and Mitochondrial DNA, Stem Cells and Development, UMR 3738 CNRS, 25-28 rue du Dr. Roux, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorra","family":"Najjar","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, El Manar I, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinda","family":"Zarrouk","sequence":"additional","affiliation":[{"name":"Genomics Platform, Institut Pasteur de Tunis (IPT), Tunis-Belv\u00e9d\u00e8re, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najoua","family":"Miladi","sequence":"additional","affiliation":[{"name":"Maghreb Medical Center, El Manar III, Tunis 9000, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Laugel","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, INSERM U1112, Institut de g\u00e9n\u00e9tique m\u00e9dicale d\u2019Alsace, CRBS, 67000 Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miria","family":"Ricchetti","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Team Stability of Nuclear and Mitochondrial DNA, Stem Cells and Development, UMR 3738 CNRS, 25-28 rue du Dr. Roux, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilhem","family":"Turki","sequence":"additional","affiliation":[{"name":"LR18SP04 and Department of Child and Adolescent Neurology, National Institute Mongi Ben Hmida of Neurology, Tunis 1007, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-4775","authenticated-orcid":false,"given":"Houda","family":"Yacoub-Youssef","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, El Manar I, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/humu.21154","article-title":"Mutation update for the CSB\/ERCC6 and CSA\/ERCC8 genes involved in Cockayne syndrome","volume":"31","author":"Laugel","year":"2010","journal-title":"Hum. 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