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 micropthalmia, bilateral congenital cataracts, hearing impairment, progressive somatic and neurodevelopmental arrest, and infantile spasms. She presented a massive photosensitive reaction with erythema and blistering after minimal sun exposure, which slowly gave place to small skin cancers. Her skin fibroblasts were 10-fold more sensitive than normal to UV exposure due to a severe deficiency in nucleotide excision repair. By complementation analysis, the 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 of XPG mRNA was encoded by this allele. The second, more significantly expressed XPG allele contained a 215C-->A transversion. This changed the highly conserved Pro-72 to a histidine, a substitution that would be expected to seriously impair the 3' endonuclease function of XPG in nucleotide excision repair. In cases suspected of having XP and/or early-onset Cockayne syndrome, extensive DNA repair studies should be performed to reach a correct diagnosis, thereby allowing reliable genetic counseling and prenatal diagnosis.
Zafeiriou
D I
DI
First Department of Pediatrics, Aristotle University of Thessaloniki, Greece.
Thorel
F
F
Andreou
A
A
Kleijer
W J
WJ
Raams
A
A
Garritsen
V H
VH
Gombakis
N
N
Jaspers
N G
NG
Clarkson
S G
SG
D000483:Alleles; D003057:Cockayne Syndrome / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases; D005260:Female; D006801:Humans; D007223:Infant; D009154:Mutation; D009687:Nuclear Proteins; D014157:Transcription Factors; D014983:Xeroderma Pigmentosum / Q000235:genetics; D000099250:DNA Excision Repair Protein ERCC-5
D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5