Xeroderma pigmentosum group G with severe neurological involvement and features of Cockayne syndrome in infancy

We describe a premature, small for gestational age infant girl with micropt halmia, bilateral congenital cataracts, hearing impairment, progressive som atic and neurodevelopmental arrest, and infantile spasms. She presented a m assive photosensitive reaction with erythema and blistering after minimal s un exposure, which slowly gave place to small skin cancers. Her skin fibrob lasts were 10-fold more sensitive than normal to UV exposure due to a sever e deficiency in nucleotide excision repair. By complementation analysis, th e patient XPCS4RO was assigned to the very rare xeroderma pigmentosum (XP) group G (XP-G). One allele of her XPG gene contained a 526C-->T transition that changed Gln-176 to a premature UAG stop codon. Only a minor fraction o f XPG mRNA was encoded by this allele. The second, more significantly expre ssed XPG allele contained a 215C-->A transversion. This changed the highly conserved Pro-72 to a histidine, a substitution that would be expected to s eriously impair the 3' endonuclease function of XPG in nucleotide excision repair. In cases suspected of having XP and/or early-onset Cockayne syndrom e, extensive DNA repair studies should be performed to reach a correct diag nosis, thereby allowing reliable genetic counseling and prenatal diagnosis.