一种新的HLA - C等位基因，其外显子3存在可变剪接位点：HLA - C*03:23N。

A new HLA-C allele with an alternative splice site in exon 3: HLA-C*03:23N.

作者信息

Shimizu Marie, Kuroda Yukari, Uchida Miyuki, Takada Shinnosuke, Kamada Hiromi, Takahashi Daisuke, Nakajima Fumiaki, Miyata Shigeki, Igarashi Shigeru, Satake Masahiro

机构信息

Central Blood Institute, Japanese Red Cross Society, Tokyo, Japan.

Kyushu Block Blood Center, Japanese Red Cross Society, Fukuoka, Japan.

出版信息

HLA. 2020 Jun;95(6):555-560. doi: 10.1111/tan.13832. Epub 2020 Feb 14.

DOI:10.1111/tan.13832

PMID:32034867

Abstract

We identified a probable new null HLA-C allele, C03:23N, which originated from C03:04:01:02, but does not react with Cw3 antibodies. This allele was identified by sequence analysis, which indicated that a single G-to-A substitution at position 406 in exon 3 created a null allele under a new mechanism: the mutation changes the position of the intron 2-exon 3 splice site to be further into exon 3, leading to a frameshift and a premature stop codon. Sequence analysis of cDNA confirmed the existence of the causative alternative acceptor splice site and the resultant deletion of 64 nucleotides in exon 3. Analysis of 220 blood or bone marrow donors in Japan with C03:23N demonstrated that Japanese HLA-C03:23N is on the haplotype A26:01∼C03:23N∼B40:02∼DRB109:01.

摘要

我们鉴定出一个可能的新的无效HLA - C等位基因C03:23N，它起源于C03:04:01:02，但不与Cw3抗体发生反应。该等位基因通过序列分析得以鉴定，结果表明外显子3中第406位的单个G到A替换通过一种新机制产生了一个无效等位基因：该突变将内含子2 - 外显子3剪接位点的位置改变至更靠近外显子3内部，导致移码和提前终止密码子。cDNA的序列分析证实了致病的可变受体剪接位点的存在以及外显子3中64个核苷酸的缺失。对日本220名携带C03:23N的血液或骨髓供体的分析表明，日本HLA - C03:23N存在于单倍型A26:01∼C03:23N∼B40:02∼DRB109:01上。