title: A novel DNA repair disorder with thrombocytopenia, nephrosis and features overlapping Cockayne syndrome.
abstract: We report on four siblings with Cockayne-like syndrome with thrombocytopenia and nephrotic syndrome. The parents were healthy and consanguineous, consistent with an autosomal recessive mode of disease inheritance. UV irradiation of fibroblasts revealed an intermediate sensitivity between normal and standard Cockayne syndrome (CS) control cells. A genome-wide linkage scan conducted using Affymetrix 10K arrays provided exclusion of the known CS genes in the family, and evidence that the disease gene maps to 1p33-p31.1. Thrombocytopenia has not previously been linked with CS, but two patients with CS in association with nephrotic syndrome have previously been documented and the phenotypes are compared with the patients described here. We suggest that this Cockayne-like phenotype with thrombocytopenia and nephrotic syndrome may be a novel DNA repair disorder, and propose that further investigation of other affected families may help identify the causative genetic defect.
authors.affiliation: North West Thames Regional Genetics Service, The North West London Hospitals NHS Trust Harrow, Middlesex, United Kingdom. e.wakeling@imperial.ac.uk
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Forsythe
authors.forename: Ruth
authors.initials: R
authors.lastname: Wild
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Sellick
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Alan R
authors.initials: AR
authors.lastname: Lehmann
authors.forename: Emma
authors.initials: E
authors.lastname: Wakeling
mesh_terms: D002648:Child; D002675:Child, Preschool; D003057:Cockayne Syndrome / Q000150:complications* / Q000235:genetics / Q000473:pathology; D004260:DNA Repair / Q000235:genetics; D049914:DNA Repair-Deficiency Disorders / Q000150:complications* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009401:Nephrosis / Q000150:complications* / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D035781:Siblings; D013577:Syndrome; D013921:Thrombocytopenia / Q000150:complications* / Q000235:genetics