Red Cell Pathology and Hematopoietic Disorders, Institute for Leukaemia Research Josep Carreras, 08916 Badalona, Spain.
Pediatric Hematology Department, University Hospital Mútua Terrassa Terrassa, 08221 Barcelona, Spain.
Cells. 2022 Mar 28;11(7):1133. doi: 10.3390/cells11071133.
Background: Hereditary spherocytosis (HS) and pyruvate kinase deficiency (PKD) are the most common causes of hereditary chronic hemolytic anemia. Here, we describe clinical and genetic characteristics of a Spanish family with concomitant β-spectrin (SPTB) c.647G>A variant and pyruvate kinase (PKLR) c.1706G>A variant. Methods: A family of 11 members was studied. Hematological investigation, hemolysis tests, and specific red cell studies were performed in all family members, according to conventional procedures. An ektacytometric study was performed using the osmoscan module of the Lorca ektacytometer (MaxSis. RR Mechatronics). The presence of the SPTB and PKLR variants was confirmed by t-NGS. Results: The t-NGS genetic characterization of the 11 family members showed the presence of a heterozygous mutation for the β-spectrin (SPTB; c.647G>A) in seven members with HS, three of them co-inherited the PKLR variant c.1706G>A. In the remaining four members, no gene mutation was found. Ektacytometry allowed a clear diagnostic orientation of HS, independently from the PKLR variant. Conclusions: This family study allows concluding that the SPTB mutation, (c.647G>A) previously described as likely pathogenic (LP), should be classified as pathogenic (P), according to the recommendations for pathogenicity of the American College of Medical Genetics and the Association for Molecular Pathology. In addition, after 6 years of clinical follow-up of the patients with HS, it can be inferred that the chronic hemolytic anemia may be attributable to the SPTB mutation only, without influence of the concomitant PKLR. Moreover, only the family members with the SPTB mutation exhibited an ektacytometric profile characteristic of HS.
遗传性球形红细胞增多症（HS）和丙酮酸激酶缺乏症（PKD）是遗传性慢性溶血性贫血的最常见原因。在这里，我们描述了一个西班牙家庭的临床和遗传特征，该家庭同时存在β- spectrin（SPTB）c.647G>A 变体和丙酮酸激酶（PKLR）c.1706G>A 变体。方法：研究了一个有 11 名成员的家庭。根据常规程序，对所有家庭成员进行了血液学检查、溶血试验和特定的红细胞研究。使用 Lorca 细胞变形计的 osmoscan 模块（MaxSis. RR Mechatronics）进行了 ektacytometric 研究。使用 t-NGS 证实了 SPTB 和 PKLR 变体的存在。结果：对 11 名家庭成员的 t-NGS 基因特征分析显示，7 名 HS 患者存在β- spectrin（SPTB；c.647G>A）杂合突变，其中 3 名患者同时携带 PKLR 变体 c.1706G>A。在其余 4 名成员中，未发现基因突变。细胞变形计能够独立于 PKLR 变体明确诊断 HS。结论：这项家族研究表明，先前被认为可能致病性（LP）的 SPTB 突变（c.647G>A）应根据美国医学遗传学学院和分子病理学协会的致病性建议归类为致病性（P）。此外，在对患有 HS 的患者进行了 6 年的临床随访后，可以推断出慢性溶血性贫血可能仅归因于 SPTB 突变，而不受同时存在的 PKLR 的影响。此外，只有携带 SPTB 突变的家庭成员表现出与 HS 特征相符的 ektacytometric 特征。
