Different impacts of alleles alphaLEPRA and alphaLELY as assessed versus a novel, virtually null allele of the SPTA1 gene in trans.
Br J Haematol
; 127(1): 118-22, 2004 Oct.
Article
em En
| MEDLINE
| ID: mdl-15384986
ABSTRACT
The family of two siblings with severe hereditary spherocytosis was investigated. The decrease was evident on both the alpha- and the beta-chains. The parents were haematologically normal. The mother was heterozygous for the low-expression polymorphic allele alphaLEPRA. The father was heterozygous for a novel combination in which one allele showed the alpha-spectrin low expression polymorphic allele alphaLELY, while his other allele showed the alphaLELY polymorphism in cis with a G-->A substitution, named Bicêtre, found at the extreme 3' end of exon 51. This combination was designated alpha(LELY-Bicêtre). The children were compound heterozygotes for alleles alphaLEPRA and alpha(LELY-Bicêtre). Reverse transcription polymerase chain reaction detected only trace amounts of the mRNA coding for alpha(LELY-Bicêtre). Mutation is therefore an essentially null mutation with no functional protein product. The lack of disease in the alphaLELY/(LELY-Bicêtre) father compared with the marked haemolysis in the alphaLEPRA/alpha(LELY-Bicêtre) children showed that expression of allele alphaLELY is not low enough to expose null alpha-spectrin alleles on the other chromosome. Quantitative estimations from these findings suggest that, to evoke spherocytosis, it is necessary that alpha-spectrin expression must be reduced to less than 25% of normal, while a reduction to 8% is sufficient.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esferocitose Hereditária
/
Espectrina
Limite:
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2004
Tipo de documento:
Article