Characterization of non-expressed C4 genes in a case of complete C4 deficiency:: Identification of a novel point mutation leading to a premature stop codon
Characterization of non-expressed C4 genes in a case of complete C4 deficiency:: Identification of a novel point mutation leading to a premature stop codon
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DOI：
10.1016/s0198-8859(98)00068-8
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发表时间：
1998-11-01
期刊：
影响因子：
2.7
通讯作者：
Truedsson, L
中科院分区：
文献类型：
--
作者：
Fredrikson, GN;Gullstrand, B;Truedsson, L
本文报告一例SLE患者C_4完全缺乏症的遗传学基础。先前的研究表明，该患者有两种不同的主要组织相容性复合体（MHC）单倍型，每种单倍型都含有一个主要缺失和一个不表达的C4基因。在本研究中，C4基因的不表达被解释为两个不同的C4基因突变的发现。在父系MHC单倍型[HLA-A2，B40，SC 00，DR 6]中检测到先前描述的C4基因外显子29中的两个碱基对插入。母体单倍型[HLA-A30，B18，F1 C 00，DR 3]携带C4基因，外显子20中有一个碱基对缺失，产生提前终止密码子。这种突变既没有发现在10个人与已知的非表达的C4基因，也没有在9个人纯合子的补体型F1 C30。对患者C4基因的同种型和同种异型特异性区域进行测序，两者均含有C4 A3 a序列。总之，类似于扩展单倍型[HLA-A2，B40，SC 02，DR 6]和[HLA-A30，B18，F1 C30，DR 3]的两种不同的MHC单倍型都含有由两种不同突变中的任一种引起的不表达的C4 A基因，证明了C4缺陷的异质性遗传背景。(C)美国组织相容性和免疫遗传学学会，1998年。出版社：Elsevier Science Inc.
The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a nonexpressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither found in 10 individuals with known non-expressed C4 genes nor in 9 individuals homozygous for the complotype F1C30. The isotype and allotype specific regions of the patient's C4 genes were sequenced, and both contained C4A3a sequence. In conclusion, two different MHC haplotypes resembling the extended haplotypes [HLA-A2, B40, SC02, DR6] and [HLA-A30, B18, F1C30, DR3] both contained a non-expressed C4A gene that was due to either of two distinct mutations, demonstrating the heterogeneous genetic background of C4 deficiency. (C) American Society for Histocompatibility and Immunogenetics, 1998. Published by Elsevier Science Inc.