HERITABLE GENETIC ALTERATIONS IN A XERODERMA-PIGMENTOSUM GROUP-G COCKAYNE-SYNDROME PEDIGREE

A search for genetic alterations within the XPG gene has been conducte d on skin and blood cells cultured from a newly characterized xeroderm a pigmentosum (XP) patient (XP20BE). This patient is the ninth known c ase that falls into the extremely rare XP complementation group G. Fou r genetic markers within the XPG gene (including two polymorphisms) de monstrated the Mendelian distribution of this gene from the parents to the patient and to an unaffected sibling. The patient (XP20BE) inheri ted a G to T transversion from his father in exon I of the XPG gene th at resulted in the conversion of a glutamic acid at codon 11 to a term ination codon. The patient also inherited an XP-G allele from his moth er that produces an unstable or poorly expressed message. The cause of the latter defect is still uncertain. In addition to these alteration s, XP20BE cDNA contained an mRNA species with a large splicing defect that encompassed a deletion from exon 1 to exon 14. This splicing defe ct, however, appears to be a naturally occurring low-frequency event t hat results from abnormal splicing that occurs between certain conserv ed non-consensus splicing signals within the human XPG gene. (C) 1997 Elsevier Science B.V.