Variable clinical severity of Hb E beta-thalassemia among Indians.
OBJECTIVE
The aim of this preliminary report was to look at the effect of genetic variations in the alpha, beta and gamma globin genes in 7 cases of hemoglobin E/beta-thalassemia with diverse clinical expression of the disease.


METHODS
beta-thalassemia mutations were characterized by PCR and dot blot hybridization. G gamma gene polymorphism (Xmnl) was determined by PCR followed by restriction enzyme digestion and polyacrylamide gel electrophoresis. alpha genotyping was done by Southern blot hybridization.


RESULTS
Six cases had a severe beta+ mutation [IVS 1 nt 5 (G-->C)] and one case had a beta zero mutation [F/S 41/42 (-CTTT)]. Hence, the beta-thalassemia mutation does not seem to contribute towards the clinical diversity. alpha-genotyping showed a single alpha-gene deletion of the rightward type in three of the five milder cases. The -158 G gamma (C-->T) substitution was present at least in heterozygous state (+/-) in all the milder cases.


CONCLUSIONS
Deletional alpha thalassemia and presence of the -158 G gamma (C->T) substitution are the two factors which appear to be more important in decreasing the severity of the disease rather than the nature of the beta thalassemia mutation.
Nadkarni
A
A
Dept. of Hematogenetics, (ICMR), KEM Hospital Campus, Parel, Mumbai, India.
Ghosh
K
K
Gorakshakar
A
A
Colah
R
R
Mohanty
D
D
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005838:Genotype; D005914:Globins / Q000235:genetics; D006446:Hemoglobin E / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
D005914:Globins; D006446:Hemoglobin E