3 NONSENSE MUTATIONS RESPONSIBLE FOR GROUP-A XERODERMA-PIGMENTOSUM

被引:75
作者
SATOKATA, I
TANAKA, K
MIURA, N
NARITA, M
MIMAKI, T
SATOH, Y
KONDO, S
OKADA, Y
机构
[1] OSAKA UNIV,SCH MED,DEPT PEDIAT,OSAKA 553,JAPAN
[2] TOKYO WOMENS MED COLL,DAINI HOSP,DEPT DERMATOL,TOKYO 116,JAPAN
[3] TOKYO MED & DENT UNIV,DEPT DERMATOL,TOKYO 116,JAPAN
来源
MUTATION RESEARCH | 1992年 / 273卷 / 02期
关键词
DNA REPAIR; DESANCTIS-CACCHIONE SYNDROME; PRENATAL DIAGNOSIS; POLYMERASE CHAIN REACTION; DNA POLYMORPHISM;
D O I
10.1016/0921-8777(92)90080-M
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The molecular basis of xeroderma pigmentosum (XP) group A was studied and 3 nonsense mutations of the XP-A complementing gene (XPAC) were identified. One was a nucleotide transition altering the Arg-228 codon (CGA) to a nonsense codon (TGA). This transition creates a new cleavage site for the restriction endonuclease HphI. Of 21 unrelated Japanese XP-A patients examined, 1 (XP39OS) was a homozygote for this mutation and 3 were compound heterozygotes for this mutation and for the splicing mutation of intron 3 reported previously which is the most common mutation in Japanese patients and creates a new cleavage site for the restriction endonuclease AlwNI. The second mutation was a nucleotide transition altering the Arg-207 codon (CGA) to a nonsense codon (TGA). A Palestinian patient (XP12RO) who had severe symptoms of XP was homozygous for this mutation. The third mutation was a nucleotide transversion altering the Tyr-116 codon (TAT) to a nonsense codon (TAA). This transversion creates a new cleavage site for the restriction endonuclease MseI. Of the Japanese patients, 2 with severe clinical symptoms had this mutant allele. One was a compound heterozygote for this mutation and for the splicing mutation, and the other was heterozygous for this mutation and homozygous for the splicing mutation. Although most XP-A patients such as XP12RO have severe skin symptoms and neurological abnormalities of the de Sanctis-Cacchione syndrome, patient XP39OS was an atypical XP-A patient who had mild skin symptoms and minimal neurological abnormalities. Our results suggest that the clinical heterogeneity in XP-A is due to different mutations in the XPAC gene. Moreover, our data indicate that almost all Japanese cases of XP-A are caused by one or more of the 3 mutations, i.e., the splicing mutation of intron 3 and the 2 nonsense mutations of codons 116 and 228. Therefore, by restriction fragment length polymorphism analysis of PCR-amplified DNA sequences using the 3 restriction enzymes described above, rapid and reliable diagnosis of XP-A can be achieved in almost all Japanese subjects including prenatal cases and carriers.
引用
收藏
页码:193 / 202
页数:10
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