Abstract：
UNASSIGNED: In clinical practice, the majority of α-thalassaemia cases arise from deletions of the α-globin genes. However, a subset of cases is attributed to rare haemoglobin variants, which can manifest with borderline or normal screening results, potentially leading to missed diagnoses in clinical practice.
UNASSIGNED: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis.
UNASSIGNED: The five-month-old proband presented a haematological phenotype consistent with Hb H disease. The mother\'s haematology profile was consistent with an α-thalassaemia carrier, while the father exhibited a borderline reduction in MCV and MCH. MALDI-TOF identified an abnormal α-chain in the proband. DNA analysis revealed a novel α-globin variant (HBA2:c.175C>A, α58His>Asn, Hb DG-Nancheng) affecting the distal histidine in the family. The father and the mother had α-genotype of --SEA/αα and αDG-Nanchengα/αα, respectively; while the proband inherited both mutant alleles (--SEA/αDG-Nanchengα). Sequencing of cDNA from HBA2 gene identified an equal ratio of normal and mutant alleles.
UNASSIGNED: This rare case highlighted the importance of identifying rare haemoglobin variant during prenatal screening. The clinical and genetic data provides useful information on the pathogenicity of this variant and further insight into the role of distal histidine residue of α-globin.
UNASSIGNED: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis.
UNASSIGNED: The five-month-old proband presented a haematological phenotype consistent with Hb H disease. The mother\'s haematology profile was consistent with an α-thalassaemia carrier, while the father exhibited a borderline reduction in MCV and MCH. MALDI-TOF identified an abnormal α-chain in the proband. DNA analysis revealed a novel α-globin variant (HBA2:c.175C>A, α58His>Asn, Hb DG-Nancheng) affecting the distal histidine in the family. The father and the mother had α-genotype of --SEA/αα and αDG-Nanchengα/αα, respectively; while the proband inherited both mutant alleles (--SEA/αDG-Nanchengα). Sequencing of cDNA from HBA2 gene identified an equal ratio of normal and mutant alleles.
UNASSIGNED: This rare case highlighted the importance of identifying rare haemoglobin variant during prenatal screening. The clinical and genetic data provides useful information on the pathogenicity of this variant and further insight into the role of distal histidine residue of α-globin.
摘要：
■在临床实践中，大多数α-地中海贫血病例是由α-珠蛋白基因缺失引起的。然而,一部分病例归因于罕见的血红蛋白变异，可以用临界或正常的筛查结果表现出来，在临床实践中可能导致漏诊。
■从家庭成员收集血液样本，并接受血液学检查，DNA和RNA分析。
■5个月大的先证者表现出符合HbH病的血液学表型。母亲的血液学特征与α-地中海贫血携带者一致，而父亲表现出MCV和MCH的临界减少。MALDI-TOF在先证中鉴定出异常的α链。DNA分析揭示了一种新的α-珠蛋白变体（HBA2：c.175C>A，α58His>Asn,HbDG-南城）影响家族中的远端组氨酸。父亲和母亲的α基因型为-SEA/αα和αDG-南城α/α，分别；而先证者遗传了两个突变等位基因(--SEA/αDG-南城α)。HBA2基因的cDNA测序鉴定出正常和突变等位基因的比例相等。
■这一罕见病例突出了在产前筛查中识别罕见血红蛋白变异的重要性。临床和遗传数据提供了有关该变体的致病性的有用信息，并进一步了解了α-珠蛋白远端组氨酸残基的作用。
■从家庭成员收集血液样本，并接受血液学检查，DNA和RNA分析。
■5个月大的先证者表现出符合HbH病的血液学表型。母亲的血液学特征与α-地中海贫血携带者一致，而父亲表现出MCV和MCH的临界减少。MALDI-TOF在先证中鉴定出异常的α链。DNA分析揭示了一种新的α-珠蛋白变体（HBA2：c.175C>A，α58His>Asn,HbDG-南城）影响家族中的远端组氨酸。父亲和母亲的α基因型为-SEA/αα和αDG-南城α/α，分别；而先证者遗传了两个突变等位基因(--SEA/αDG-南城α)。HBA2基因的cDNA测序鉴定出正常和突变等位基因的比例相等。
■这一罕见病例突出了在产前筛查中识别罕见血红蛋白变异的重要性。临床和遗传数据提供了有关该变体的致病性的有用信息，并进一步了解了α-珠蛋白远端组氨酸残基的作用。
