College of Nursing, University of Cincinnati, Cincinnati, Ohio.
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Pediatr Blood Cancer. 2019 Feb;66(2):e27531. doi: 10.1002/pbc.27531. Epub 2018 Nov 4.
The broad phenotypic variability among individuals with sickle cell disease (SCD) suggests the presence of modifying factors. We identified two unrelated SCD patients with unusually severe clinical and laboratory phenotype that were found to carry the hereditary elliptocytosis-associated alpha-spectrin mutation c.460_462dupTTG (p.L155dup), a mutation enriched due to positive selective pressure of malaria, similar to the SCD globin mutations. A high index of suspicion for additional hematologic abnormalities may be indicated for challenging patients with SCD. These cases highlight the validity of specialized testing such as ektacytometry and next-generation sequencing for patients and family members to assess genotype/phenotype correlations.
镰状细胞病(SCD)患者的表型广泛变异性表明存在修饰因子。我们发现两名无关的 SCD 患者具有异常严重的临床和实验室表型,他们携带遗传性椭圆形红细胞增多症相关的α- spectrin 突变 c.460_462dupTTG(p.L155dup),这种突变由于疟疾的正选择压力而丰富,类似于 SCD 珠蛋白突变。对于具有挑战性的 SCD 患者,可能需要高度怀疑存在其他血液学异常。这些病例强调了针对患者和家庭成员进行特殊测试(如 ektacytometry 和下一代测序)的有效性,以评估基因型/表型相关性。