HbAdrian(α1:c.251del,p.Leu84Argfs*19)——伊朗北部与微细胞增多症相关的α1-球蛋白基因的一种新的致病性变体

IF 0.6 Q4 HEMATOLOGY Thalassemia Reports Pub Date : 2023-06-01 DOI:10.3390/thalassrep13020014
H. Jalali, H. Karami, Mahan Mahdavi, M. Mahdavi
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引用次数: 0

摘要

背景:地中海贫血是人类最常见的遗传异常之一。已经引入了400多种不同的α-珠蛋白变体,其中大多数与明显的临床表现无关。识别不同地区Hb的所有变体有助于获得有关地中海贫血疾病的全面知识,并可用于预防计划和产前诊断(PND)。目的:在本研究中,我们描述了一种新的α1基因突变,该突变导致密码子83后的移码。方法:作为国家地中海贫血筛查计划的一部分,应用常规细胞计数(CBC)和Hb毛细管电泳检测。在取得书面知情同意书后,提取基因组DNA,并进行多重Gap PCR以鉴定常见的地中海α-球蛋白基因缺失;为了检测α-和β-球蛋白基因的其他突变,使用了DNA测序方法。结果:CBC和毛细管电泳检测结果显示一名女性受试者存在微细胞增多症。α-球蛋白基因的测序表明,该病例为杂合子,其α1-球蛋白基因第83密码子处的单核苷酸缺失。我们将这种突变命名为Hb Adrian(α1:c.251–T),这是一种新的突变。在受试者的母亲身上也检测到了上述突变。结论:引入的突变(Hb Adrian)导致移码改变,产生一种具有100个氨基酸的蛋白质,与正常的α链相比,该蛋白质更短,并且其氨基酸在密码子83后发生改变。这种血红蛋白是无法通过电泳检测到的。尽管在携带者中没有观察到主要的血液学异常,但在筛查项目中应考虑Hb Adrian,以帮助预防高危夫妇的Hb H疾病。
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HbAdrian (α1:c.251del, p.Leu84Argfs*19)—A Novel Pathogenic Variant in the α1-Globin Gene Associated with Microcytosis from the North of Iran
Background: Alpha thalassemia is one of the most common human genetic abnormalities. More than 400 different variations of the α-globin protein have been introduced, most of which are not associated with noticeable clinical manifestations. The identification of all variants of Hb in different regions helps in acquiring comprehensive knowledge concerning thalassemia disease, and it can be used in preventive programs as well as prenatal diagnosis (PND). Aims: In the present study, we describe a new α1 gene mutation that leads to a frameshift after codon 83. Methods: As a plan for a national screening program of thalassemia, routine cell blood count (CBC) and Hb capillary electrophoresis tests were applied. After taking written informed consent, genomic DNA was extracted, and, for identifying common Mediterranean α-Globin gene deletion, multiplex Gap-PCR was performed; for detecting other mutations on α- and β-Globin genes, a DNA sequencing method was used. Results: The results of CBC and capillary electrophoresis tests showed microcytosis in a female subject. The sequencing of the α-Globin gene showed that the case is heterozygote for a single-nucleotide deletion at codon 83 of the α1-Globin Gene. We named this mutation Hb Adrian (α1: c.251–T), which is a novel mutation. The mentioned mutation was also detected in the subject’s mother. Conclusions: The introduced mutation (Hb Adrian) leads to a frameshift change that produces a protein with 100 amino acids, which in comparison to a normal α-chain is shorter, and its amino acids are altered after codon 83. This hemoglobin is undetectable via the use of electrophoresis. Although no major hematological abnormalities were observed in the carriers, Hb Adrian should be considered in screening programs to help prevent Hb H disease in high-risk couples.
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来源期刊
Thalassemia Reports
Thalassemia Reports HEMATOLOGY-
自引率
0.00%
发文量
17
审稿时长
10 weeks
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