Two siblings with unusually mild homozygous β-thalassemia: A didactic example of the effect of a nonallelic modifier gene on the expressivity of a monogenic disorder
✍ Scribed by Prchal, Josef ;Stamatoyannopoulos, G. ;Opitz, John M.
- Publisher
- John Wiley and Sons
- Year
- 1981
- Tongue
- English
- Weight
- 655 KB
- Volume
- 10
- Category
- Article
- ISSN
- 0148-7299
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✦ Synopsis
Abstract
Two adult Black sibs with homozygous β‐thalassemia had severe deficiency of β‐chain production but an unusually mild clinical course and almost normal hematocrit values. Their father had the typical hematological findings of β‐thalassemia trait but the mother, in addition to the β‐thalassemia trait, had elevated F cells (42.2%). Elevated F cells were also present in a hematologically normal sister of the affected providing evidence that a gene for heterocellular hereditary persistence of fetal hemoglobin (HPFH) was also running in this family. The unusually mild clinical course of the two homozygotes is attributed to their inheritance from their mother of the heterocellular HPFH gene. The gene for heterocellular HPFH is nonallelic to the β‐globin locus and apparently acted as a modifier of the homozygous β‐thalassemia phenotype by facilitating F‐cell production and thus diminishing the pathophysiological consequences of the β‐thalassemia defect. The effect of heterocellular HPFH on the expression of homozygous β‐thalassemia or Hb S genotypes is an impressive example of the pathophysiological basis of changes in the expressivity of monogenic disorders due to action of nonallelic modifiers.