Abstract:
Objective To analyse potential genetic cause of a family affected with hereditary elliptocytosis （HE）.
Methods Peripheral blood samples from this HE family were collected. Targeted capture and high-throughput sequencing of 4 813 genetic disease-associated genes was performed in four members of the family. Possible causative genetic variation was obtained and further confirmed by Sanger sequencing. Fifty healthy control subjects were recruited for detection of the candidate variation.
Results High-throughput sequencing detected a nonsense mutation c.1215G>A（p.Trp405Ter）in exon 13 of the EPB41 gene in the proband and his mother presenting with moderate anemia. The pathogenicity of this loss-of-function mutation is very strong, because the G→A transition leads to introduce the premature stop codon instead of tryptophan codon at position 405, which producing a truncating protein with loss of important functional domains. This causative mutation is extremely rare in the population, and it has not yet been reported. The grandmother of the proband was heterozygous for the same mutation. Genotype-phenotype cosegregation was observed in this family. This mutation was not found in the 50 unrelated healthy controls.
Conclusion The c.1215G>A mutation of the EPB41 gene probably accounts for the disease in this HE family. This study reports a pathogenic EPB41 mutation in a Chinese HE family for the first time.
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