title: ERCC6 dysfunction presenting as progressive neurological decline with brain hypomyelination.
abstract: Mutations in ERCC6 are associated with growth failure, intellectual disability, neurological dysfunction and deterioration, premature aging, and photosensitivity. We describe siblings with biallelic ERCC6 mutations (NM_000124.2:c. [543+4delA];[2008C>T]) and brain hypomyelination, microcephaly, cognitive decline, and skill regression but without photosensitivity or progeria. DNA repair assays on cultured skin fibroblasts confirmed a defect of transcription-coupled nucleotide excision repair and increased ultraviolet light sensitivity. This report expands the disease spectrum associated with ERCC6 mutations.
authors.affiliation: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH and National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors.forename: Laila
authors.initials: L
authors.lastname: Shehata
authors.forename: Dimitre R
authors.initials: DR
authors.lastname: Simeonov
authors.forename: Anja
authors.initials: A
authors.lastname: Raams
authors.forename: Lynne
authors.initials: L
authors.lastname: Wolfe
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.forename: Xueli
authors.initials: X
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Shannon
authors.initials: S
authors.lastname: Garner
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: Audrey
authors.initials: A
authors.lastname: Thurm
authors.forename: Gail E
authors.initials: GE
authors.lastname: Herman
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Tifft
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Nicolaas G J
authors.initials: NG
authors.lastname: Jaspers
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D017398:Alternative Splicing; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D019066:Facies; D005260:Female; D015870:Gene Expression; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007438:Introns; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000075223:Poly-ADP-Ribose Binding Proteins; D035781:Siblings
chemical_list: D015415:Biomarkers; D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes
keywords: Cockayne syndrome group B; deafness; developmental delay; hypomyelination; intellectual disability; vision loss