A genomic deletion causes truncation of α-spectrin and ellipto-poikilocytosis.

We report on a truncated α-spectrin chain, spectrin(Exeter), associated with ellipto-poikilocytosis. Analysis of erythrocyte membranes of affected individuals revealed a truncated α-spectrin chain with normal amounts of spectrin dimer. In the proband and her father, one haploid set of α-spectrin cDNA lacked exons 11 and 12, leading to partial deletion of repeats α4 and α5 (83 amino acids) of the α-spectrin chain. In one allele of genomic DNA, a 3567bp deletion starting in intron 10 and ending in intron 12 of the SPTA1 gene was found. The common polymorphic SPTA1 α(LELY) allele was found in trans to the SPTA1αExeter allele in the proband. The proband had inherited the SPTA1Exeter allele from her father and the αLELY allele from her healthy, asymptomatic mother. This is the first report of an interstitial deletion in the SPTA1 gene associated with ellipto-poikilocytosis.

Hereditary spherocytosis.

Hereditary spherocytosis is a common hemolytic disorder characterized by a defect or deficiency in one or more of the proteins composing red blood cell membrane. As a result, red blood cells have an abnormal shape, higher metabolic requirements, and are prematurely trapped and destroyed in the spleen. Hereditary spherocytosis, including the very mild or subclinical forms, is the most common cause of non-immune hemolytic anemia among people of Northern European ancestry, with a prevalence of approximately 1 in 2000. However very mild forms of the disease may be much more common. Hereditary spherocytosis is inherited in a dominant fashion in 75% of cases, whereas the remaining are truly recessive cases and de novo mutations. This review reports current concepts on red cell membrane structure and it will attempt to clarify molecular defects leading to spherocyte and their consequences.