Heritable genetic alterations in a xeroderma pigmentosum group G/Cockayne syndrome pedigree

A search for genetic alterations within the XPG gene has been conducted on skin and blood cells cultured from a newly characterized xeroderma pigmentosum (XP) patient (XP20BE). This patient is the ninth known case that falls into the extremely rare XP complementation group G. Four genetic markers within the XPG gene (including two polymorphisms) demonstrated the Mendelian distribution of this gene from the parents to the patient and to an unaffected sibling. The patient (XP20BE) inherited a G to T transversion from his father in exon 1 of the XPG gene that resulted in the conversion of a glutamic acid at codon 11 to a termination codon. The patient also inherited an XP-G allele from his mother that produces an unstable or poorly expressed message. The cause of the latter defect is still uncertain. In addition to these alterations, XP20BE cDNA contained an mRNA species with a large splicing defect that encompassed a deletion from exon 1 to exon 14. This splicing defect, however, appears to be a naturally occurring low-frequency event that results from abnormal splicing that occurs between certain conserved non-consensus splicing signals within the human XPG gene.