一种针对中国人血红蛋白H病基因分型的实验室策略。

A laboratory strategy for genotyping haemoglobin H disease in the Chinese.

作者信息

Chan Amy Yuk-Yin, So Chi-Chiu, Ma Edmond Shiu-Kwan, Chan Li-Chong

机构信息

Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.

出版信息

J Clin Pathol. 2007 Aug;60(8):931-4. doi: 10.1136/jcp.2006.042242. Epub 2006 Oct 3.

DOI:10.1136/jcp.2006.042242

PMID:17018682

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1994485/

Abstract

BACKGROUND

The thalassaemias are the commonest blood disorders worldwide, with South East Asia and southern China as areas of high prevalence. Accurate diagnosis of these disorders helps in clinical management with improved outcome.

METHODS

The alpha-globin genotypes of 100 Chinese patients in Hong Kong with haemoglobin H (Hb H) disease were characterised. Single-tube multiplex gap-PCR was used to detect --(SEA), -alpha(3.7) and -alpha(4.2), while Hb CS, Hb QS and codon 30 (DeltaGAG) were identified by single-tube multiplex amplification refractory mutation system (ARMS). Automated direct nucleotide sequencing of the amplified alpha2- and alpha1-globin genes was performed to characterise other non-deletional alpha-thalassaemia determinants.

RESULTS

In the 100 cases studied, 99 cases had --(SEA) in combination with deletional alpha(+)-thalassaemia or non-deletional alpha-globin gene mutation involving the alpha2-globin gene. In 70 cases of the deletional form, 43 cases showed the genotype of (--(SEA)/-alpha(3.7)) and 27 cases of (--(SEA)/-alpha(4.2)). Three of the 27 cases of (--(SEA)/-alpha(4.2)) were found to have Hb Q-Thailand linked in-cis with -alpha(4.2). The remaining 30 cases were of non-deletional form with the following genotypes: 11 cases of (--(SEA)/alpha(HbCS)alpha), 9 cases of (--(SEA)/alpha(HbQS)alpha), 3 cases of (--(SEA)/alpha(cd30 (DeltaGAG))alpha), 3 cases of (--(SEA)/alpha(cd31)alpha), 2 cases of (--(SEA)/alpha(poly-A)alpha), 1 case of (--(SEA)/alpha(HbWestmead)alpha) and 1 case of (--(non-SEA)/alpha(HbQS)alpha).

CONCLUSIONS

Based on two rapid diagnostic tests, multiplex gap-PCR and multiplex ARMS, more than 90% of the cases were genetically characterised. This laboratory strategy should be widely applicable for genetic diagnosis of alpha-thalassaemia.

摘要

背景

地中海贫血是全球最常见的血液疾病，东南亚和中国南方是高发地区。准确诊断这些疾病有助于临床管理并改善治疗效果。

方法

对100例香港血红蛋白H（Hb H）病中国患者的α珠蛋白基因型进行了鉴定。采用单管多重缺口PCR检测--(SEA)、-α(3.7)和-α(4.2)，同时通过单管多重扩增不应性突变系统（ARMS）鉴定Hb CS、Hb QS和密码子30（DeltaGAG）。对扩增的α2和α1珠蛋白基因进行自动直接核苷酸测序，以鉴定其他非缺失型α地中海贫血决定因素。

结果

在研究的100例病例中，99例具有--(SEA)，并伴有缺失型α(+)-地中海贫血或涉及α2珠蛋白基因的非缺失型α珠蛋白基因突变。在70例缺失型病例中，43例基因型为（--(SEA)/-α(3.7)），27例为（--(SEA)/-α(4.2)）。在27例（--(SEA)/-α(4.2)）病例中，有3例发现Hb Q-泰国与-α(4.2)呈顺式连锁。其余30例为非缺失型，基因型如下：11例（--(SEA)/α(HbCS)α），9例（--(SEA)/α(HbQS)α），3例（--(SEA)/α(密码子30（DeltaGAG）)α），3例（--(SEA)/α(密码子31)α），2例（--(SEA)/α(多聚A)α），1例（--(SEA)/α(HbWestmead)α）和1例（--(非SEA)/α(HbQS)α）。