[Dominant beta-thalassemia alleles in the Czech and Slovak population (beta-thalassemia mutations in 112(T-A) and 121(G-T) codons and the unstable Hradec Králové hemoglobin or alpha 2 beta 2 115 (G17) Ala-Asp)].
In four unrelated families of Czech and Slovak origin two nonsense dominant beta-thalassaemic alleles (CD 121 (G-T); CD 112 (T-A)) and in one family simple substitution in codon 115 (GCC-GAC) or alpha 2 beta 2 115 (G17) Ala-Asp HB-Hradec Králové were identified. Mutations in codons 112 and 115 were described for the first time. Phenotypic manifestation of beta-thal. intermedia was revealed in three families with CD 121 (G-T) and in a family with a mutation in CD 112, but the phenotypic manifestations differed markedly in individual subjects. Heinz bodies were detected in erythrocytes of the peripheral blood in two families. An exact explanation of phenotypic deviations in patients with the same mutation even within the same family were not obtained even in studies of alpha genes and the promoter area of the beta gene. The unstable variant of Hb-Hradec Králové is manifested in the mother and daughter by haemolytic anaemia with some traits of beta-thal. The authors discuss contemporary findings from the pathophysiology of recessive and dominant beta-thal. mutations and explain some of the phenotypic consequences. A relatively high incidence of dominant beta-thal. mutations in the Czech and Slovak Republic (4 of 12 families known world wide with a nonsense beta-thal. mutation in the 3rd exon) is explained by the absence of selective preference of these mutations in malaria infested areas as a result of serious clinical manifestations in heterozygotes. The haplotype in one of the families suggests a de novo origin of the mutation in CD 121.
Indrák
K
K
Hematologická klinika FN a LF UP Olomouc, Indrák.
Divoký
V
V
Brabec
V
V
Chrobák
L
L
Mociková
K
K
Sakalová
A
A
Svobodová
M
M
Indráková
J
J
Hammerová
T
T
Zarnovicanová
M
M
D000328:Adult; D000368:Aged; D000483:Alleles; D002675:Child, Preschool; D003062:Codon / Q000235:genetics*; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D005799:Genes, Dominant; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D018154:Slovakia / Q000453:epidemiology; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
D003062:Codon; D006454:Hemoglobins
Dominantní beta-talasemické alely v ceské a slovenské populaci [beta-talasemické mutace v kodonech 112 (T-A) a 121 (G-T) a nestabilní hemoglobinová varianta Hradec Králové nebo alpha 2 beta 2 115 (G 17) Ala-Asp].