Abstract
The identification of individuals homozygous for a specific mutation offers advantages for the elucidation of molecular mechanisms of hereditary disease states. Cockayne syndrome is a rare autosomal recessive disorder, the molecular basis of which is complicated by significant genetic and clinical heterogeneity. The genes associated with both genetic complementation groups, CSA and CS-B, have been identified. We have previously identified a number of CSA mutations, including a single base substitution that introduces a stop codon (322Tyr→Stop) mutation in the C-terminal region for at least one allele of the CSA gene in a severely affected patient. We now present data confirming the existence of homozygosity in this patient using a strategy with general applicability. Somatic cell hybrids were established by fusing patient cells with mouse A9 cells. Screening with chromosome 5 specific polymorphic markers facilitated identification of hybrid clones bearing only one of the distinct CSA alleles. Sequencing of a portion of the human CSA gene in a subset of these hybrids permitted monoallelic mutation analysis and confirmed the presence of the 322Tyr→Stop mutation in both alleles.
Original language | English (US) |
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Pages (from-to) | 317-321 |
Number of pages | 5 |
Journal | Human mutation |
Volume | 10 |
Issue number | 4 |
DOIs | |
State | Published - 1997 |
Keywords
- Cockayne syndrome
- Homozygosity
- Mutations
- Somatic hybrids
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)