Prenatal diagnosis of Cockayne syndrome type A based on the identification of two novel mutations in the ERCC8 gene.

Back Cockayne syndrome (CS; MIM 133540-216400) is a rare autosomal recessive neurodegenerative disorder characterized by progressive growth failure, microcephaly, mental retardation, retinal pigmentary degeneration, deafness, photosensitivity, accelerated systemic degeneration of somatic tissue, and premature death. Complementation assays have defined Cockayne syndrome group A (CSA) and Cockayne syndrome group B (CSB), caused by mutations in ERCC8 and ERCC6. The aim of this work was to perform a molecular analysis in a family with an affected son, who died at the age of 12, presenting clinical features typical of CSA. Molecular analysis of ERCC8 allowed us to characterize two novel mutations: a maternally inherited deletion encompassing exons 5 and 6, and a nonsense mutation located in exon 4, segregating from the father. Based on this molecular characterization, we successively performed a prenatal diagnosis on chorionic villus sampling, at 11th week of pregnancy. Molecular prenatal analysis of the ERCC8 was done by analyzing fetal DNA and RNA, looking for both mutations identified in the proband. A linkage analysis was performed using microsatellite markers located on chromosome 5q11 with the purpose to follow the segregation of the mutated alleles within the family. The fetal genotype at CSA locus resulted wild type and was confirmed at birth on biological material isolated from placenta. This study documents for the first time a molecular prenatal diagnosis of CSA, which results in the preferred approach if the mutation within the family is identified in a timely manner.