{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:38:41Z","timestamp":1775590721762,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health with \u201cCurrent Research funds\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes ERCC6 (CS type B) and ERCC8 (CS type A). We assessed this, presenting a series of patients with genetically confirmed CSB. (2) Materials and Methods: We retrospectively collected demographic, clinical, genetic, neuroimaging, and serum neurofilament light-chain (sNFL) data about CSB patients; diagnostic and severity scores were also determined. (3) Results: Data of eight ERCC6\/CSB patients are presented. Four patients had CS I, three patients CS II, and one patient CS III. Various degrees of ataxia and spasticity were cardinal neurologic features, with variably combined systemic characteristics. Mean age at diagnosis was lower in the type II form, in which classic CS signs were more evident. Interestingly, sNFL determination appeared to reflect clinical classification. Two novel premature stop codon and one novel missense variants were identified. All CS I subjects harbored the p.Arg735Ter variant; the milder CS III subject carried the p.Leu764Ser missense change. (4) Conclusion: Our work confirms clinical variability also in the ERCC6\/CSB type, where manifestations may range from severe involvement with prenatal or neonatal onset to normal psychomotor development followed by progressive ataxia. We propose, for the first time in CS, sNFL as a useful peripheral biomarker, with increased levels compared to currently available reference values and with the potential ability to reflect disease severity.<\/jats:p>","DOI":"10.3390\/genes15040508","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T10:30:52Z","timestamp":1713436252000},"page":"508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2367-6371","authenticated-orcid":false,"given":"Jacopo","family":"Sartorelli","sequence":"first","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disease, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Travaglini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Macchiaiolo","sequence":"additional","affiliation":[{"name":"Rare Diseases and Medical Genetics Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3029-8536","authenticated-orcid":false,"given":"Giacomo","family":"Garone","sequence":"additional","affiliation":[{"name":"Neurology, Epilepsy and Movement Disorder Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"},{"name":"Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela Veronika","family":"Gonfiantini","sequence":"additional","affiliation":[{"name":"Rare Diseases and Medical Genetics Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2907-3206","authenticated-orcid":false,"given":"Davide","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Rare Diseases and Medical Genetics Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1371-936X","authenticated-orcid":false,"given":"Lorenzo","family":"Sinibaldi","sequence":"additional","affiliation":[{"name":"Rare Diseases and Medical Genetics Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flaminia","family":"Frascarelli","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viola","family":"Ceccatelli","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Petrillo","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disease, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1825-9347","authenticated-orcid":false,"given":"Fiorella","family":"Piemonte","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disease, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Piccolo","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Longo","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Imaging Department, Bambino Ges\u00f9 Children\u2019s Hospital, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6486-5201","authenticated-orcid":false,"given":"Stefano","family":"Pro","sequence":"additional","affiliation":[{"name":"Developmental Neurology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2438-2624","authenticated-orcid":false,"given":"Adele","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disease, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4590","authenticated-orcid":false,"given":"Enrico Silvio","family":"Bertini","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disease, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5612-821X","authenticated-orcid":false,"given":"Francesco","family":"Nicita","sequence":"additional","affiliation":[{"name":"Unit of Neuromuscular and Neurodegenerative Disease, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, P.zza Sant\u2019Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.mad.2013.02.006","article-title":"Cockayne syndrome: The expanding clinical and mutational spectrum","volume":"134","author":"Laugel","year":"2013","journal-title":"Mech. 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