Different impacts of alleles αLEPRA and αLELY as assessed versus a novel, virtually null allele of the SPTA1 gene in trans

• Published in: British journal of haematology Vol. 127; no. 1; pp. 118 - 122
• Main Authors: Delaunay, J., Nouyrigat, V., Proust, A., Schischmanoff, P.‐O., Cynober, T., Yvart, J., Gaillard, C., Danos, O., Tchernia, G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-10-2004; Blackwell
• Subjects: allele αLELY; allele αLEPRA; Anemias. Hemoglobinopathies; Biological and medical sciences; Diseases of red blood cells; exon 51 mutation; Hematologic and hematopoietic diseases; hereditary spherocytosis; Medical sciences; SPTA1 gene; Erythrocytic membrane disease; Hematology; hereditary spherocytosis; Silent allele; Hemopathy; allele αLELY; Spherocytic anemia; Genetic disease; Hemolytic anemia; Exon; Gene; SPTA1 gene; allele αLEPRA; Genetics; Mutation; Comparative study; exon 51 mutation
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2004.05160.x

Summary
The family of two siblings with severe hereditary spherocytosis was investigated. The decrease was evident on both the α‐ and the β‐chains. The parents were haematologically normal. The mother was heterozygous for the low‐expression polymorphic allele αLEPRA. The father was heterozygous for a novel combination in which one allele showed the α‐spectrin low expression polymorphic alleleαLELY, while his other allele showed the αLELY polymorphism in cis with a G→A substitution, named Bicêtre, found at the extreme 3′ end of exon 51. This combination was designated . The children were compound heterozygotes for alleles αLEPRA and . Reverse transcription polymerase chain reaction detected only trace amounts of the mRNA coding for . Mutation is therefore an essentially null mutation with no functional protein product. The lack of disease in the αLELY/ father compared with the marked haemolysis in the αLEPRA/ children showed that expression of allele αLELY is not low enough to expose null α‐spectrin alleles on the other chromosome. Quantitative estimations from these findings suggest that, to evoke spherocytosis, it is necessary that α‐spectrin expression must be reduced to less than 25% of normal, while a reduction to 8% is sufficient.