中国西南地区缺失型遗传性胎儿血红蛋白持续存在/δβ-地中海贫血和 δ-珠蛋白基因突变分析。

Analysis of deletional hereditary persistence of fetal hemoglobin/δβ-thalassemia and δ-globin gene mutations in Southerwestern China.

机构信息

Department of Obstetrics and Gynecology, The First People's Hospital of Yunnan Province, Kunming, China.

Genetic Diagnosis Center, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, The First People's Hospital of Yunnan Province, Kunming, China.

出版信息

Mol Genet Genomic Med. 2019 Jun;7(6):e706. doi: 10.1002/mgg3.706. Epub 2019 May 1.

DOI:10.1002/mgg3.706

PMID:31044540

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6565566/

Abstract

BACKGROUND

Deletional hereditary persistence of fetal hemoglobin (HPFH)/δβ-thalassemia and δ-thalassemia are rare inherited disorders which may complicate the diagnosis of β-thalassemia. The aim of this study was to reveal the frequency of these two disorders in Southwestern China.

METHODS

A total of 33,596 subjects were enrolled for deletional HPFH/δβ-thalassemia, and positive individuals with high fetal hemoglobin (Hb F) level were diagnosed by multiplex ligation-dependent probe amplification (MLPA). A total of 17,834 subjects were analyzed for mutations in the δ-globin gene. Positive samples with low Hb A levels were confirmed by δ-globin gene sequencing. Furthermore, the pathogenicity and construction of a selected δ-globin mutation were analyzed.

RESULTS

A total of 92 suspected cases with Hb F ≥5.0% were further characterized by MLPA. Eight different deletional HPFH/δβ-thalassemia were observed at a frequency of 0.024%. In addition, 195 cases suspected to have a δ-globin gene mutation (Hb A ≤2.0%) were characterized by molecular analysis. δ-Globin gene mutation was found at a frequency of 0.49% in Yunnan. The pathogenicity and construction for a selected δ-globin mutation was predicted.

CONCLUSION

Screening of these two disorders was analyzed in Southwestern China, which could define the molecular basis of these conditions in this population.

摘要

背景

缺失型遗传性胎儿血红蛋白持续存在（HPFH）/δβ-地中海贫血和 δ-地中海贫血是罕见的遗传性疾病，可能使β-地中海贫血的诊断复杂化。本研究旨在揭示这两种疾病在中国西南部的发生率。

方法

共纳入 33596 例个体进行缺失型 HPFH/δβ-地中海贫血的筛查，对高胎儿血红蛋白（Hb F）水平的阳性个体采用多重连接依赖性探针扩增（MLPA）进行诊断。对 17834 例个体进行 δ-珠蛋白基因突变分析。Hb A 水平低的阳性样本通过 δ-珠蛋白基因测序进行确认。此外，还对选定的 δ-珠蛋白突变的致病性和构建进行了分析。

结果

共对 92 例 Hb F≥5.0%的疑似病例进行了 MLPA 进一步分析。观察到 8 种不同的缺失型 HPFH/δβ-地中海贫血，发生率为 0.024%。此外，对 195 例疑似 δ-珠蛋白基因突变（Hb A≤2.0%）的个体进行了分子分析。在云南，δ-珠蛋白基因突变的发生率为 0.49%。对选定的 δ-珠蛋白突变的致病性和构建进行了预测。