A stop codon in xeroderma pigmentosum group C families in Turkey and Italy: Molecular genetic evidence for a common ancestor
Küçük Resim Yok
Tarih
2001
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Blackwell Science Inc
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Xeroderma pigmentosum family G from Van, Turkey had two severely affected children: a son with multiple skin cancers who died at age 10 (XP67TMA), and an 8 y old daughter who began developing skin cancer before 3 y of age (XP68TMA). XP67TMA and XP68TMA cells were hypersensitive to killing by ultraviolet and the post-ultraviolet DNA repair level was 12-16% of normal. Host cell reactivation of an ultraviolet-treated reporter plasmid cotransfected with a vector expressing wild-type XPC cDNA assigned XP67TMA to xeroderma pigmentosum complementation group C. The XPC mRNA level was markedly reduced. Sequencing of the 3.5 kb XPC cDNA from XP67TMA showed a C-T mutation in XPC exon 8 at base pair 1840. This mutation converts the CGA codon of arginine at amino acid 579 to a UGA stop codon resulting in marked truncation of the 940 amino acid xeroderma pigmentosum C protein. Restriction fragment length polymorphism analysis of XPC exon 8 DNA in XP67TMA and XP68TMA showed that both affected children had a homozygous mutation and that both parents had heterozygous normal and mutated sequences at the same position consistent with a history of consanguinity in the family. The mutated allele also contained two XPC single nucleotide polymorphisms. The same mutated XPC allele was reported in an Italian family. Studies of 19 microsatellite markers flanking the XPC gene on chromosome 3 suggest that the XPC allele passed between Italy and Turkey approximately 300-500 y ago. This XPC allele containing a nonsense mutation is associated with severe clinical disease with multiple skin cancers and early death.
Açıklama
Anahtar Kelimeler
DNA repair, microsatellite markers, skin cancer, SNP, UV radiation
Kaynak
Journal of Investigative Dermatology
WoS Q Değeri
Q1
Scopus Q Değeri
Cilt
117
Sayı
2
