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Different impacts of alleles α LEPRA and α LELY as assessed versus a novel, virtually null allele of the SPTA1 gene in trans
Author(s) -
Delaunay J.,
Nouyrigat V.,
Proust A.,
Schischmanoff P.O.,
Cynober T.,
Yvart J.,
Gaillard C.,
Danos O.,
Tchernia G.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05160.x
Subject(s) - null allele , allele , biology , genetics , microbiology and biotechnology , alpha (finance) , gene , medicine , construct validity , nursing , patient satisfaction
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 α LEPRA . The father was heterozygous for a novel combination in which one allele showed the α ‐spectrin low expression polymorphic allele α LELY , while his other allele showed the α LELY 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 α LEPRA 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 α LELY / father compared with the marked haemolysis in the α LEPRA / children showed that expression of allele α LELY 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.