title: A novel splice site mutation in the Cockayne syndrome group A gene in two siblings with Cockayne syndrome.
abstract: Cockayne syndrome (CS) is mainly caused by mutations in the Cockayne syndrome group A or B (CSA or CSB) genes which are required for a sub-pathway of nucleotide excision repair entitled transcription coupled repair. Approximately 20% of the CS patients have mutations in CSA, which encodes a 44 kDa tryptophane (Trp, W) and aspartic acid (Asp, D) amino acids (WD) repeat protein. Up to now, nine different CSA mutations have been identified. We examined two Somali siblings 9 and 12 years old with clinical features typical of CS including skin photosensitivity, progressive ataxia, spasticity, hearing loss, central and peripheral demyelination and intracranial calcifications. Molecular analysis showed a novel splice acceptor site mutation, a G to A transition in the -1 position of intervening sequence 6 (g.IVS6-1G>A), in the CSA (excision repair cross-complementing 8 (ERCC8)) gene. IVS6-1G>A results in a new 28 amino acid C-terminus and premature termination of the CSA protein (G184DFs28X). A review of the CSA protein and the 10 known CSA mutations is also presented.
authors.affiliation: Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, Rikshospitalet-Radiumhospitalet HF, University of Oslo, N-0027 Oslo, Norway. liv.kleppa@medisin.uio.no
authors.forename: L
authors.initials: L
authors.lastname: Kleppa
authors.forename: Ø J
authors.initials: ØJ
authors.lastname: Kanavin
authors.forename: A
authors.initials: A
authors.lastname: Klungland
authors.forename: P
authors.initials: P
authors.lastname: Strømme
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000473:pathology; D002648:Child; D003057:Cockayne Syndrome / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D012998:Somalia; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C095472:ERCC8 protein, human; D005819:Genetic Markers; D022821:RNA Splice Sites; D014157:Transcription Factors; D045643:DNA Repair Enzymes