An α‐Thalassemia Phenotype in a Dutch Hindustani, Caused by a New Point Mutation that Creates an Alternative Splice Donor Site in the First Exon of the α2‐Globin Gene

Abstract

The proband is an elderly woman (79 years of age) of Surinamese–Hindustani origin, suspected of being a carrier of a nondeletional α‐thalassemia (thal) because of a moderate microcytic hypochromic anemia at normal ferritin levels and in the absence of any other α‐thal deletions. Sequence analysis revealed a silent mutation (GGC→GGT) at codon 22 of the α2‐globin gene. This mutation generates a splice donor site consensus sequence (GGTGAG) between codons 22 and 23. The abnormally spliced mRNA leads to a premature termination between codons 48 and 49. The presence of a downstream intron may induce the intracellular degradation of the affected mRNA, a pathway known as nonsense mediated decay (NMD), and this explains the α⁺‐thal phenotype observed in the patient. The codon 22 (GGC→GGT) transition described in this report is the first mutation creating a splice donor site in one of the α‐globin genes.

• Nondeletional α‐thalassemia (thal)
• α‐Globin gene
• Nonsense mediated decay (NMD)
• Splice donor site
• Premature termination