Hb H disease in a Turkish family resulting from the interaction of a deletional alpha-thalassaemia-1 and a newly discovered poly A mutation.
We have analysed the alpha-globin gene defects present in several members of a large family from Southern Turkey. One deletional alpha-thalassaemia-1 (type MED-II) was found in 10 subjects: this deletion is in excess of 26.5 kb and includes all zeta- and alpha-globin genes. Besides the common types of deletional alpha-thalassaemia-2 (-3.7 kb and -4.2 kb) we observed a nondeletional alpha-thalassaemia-2 that results from an A----G mutation (AATAAA----AATGAA) in the polyadenylation signal of the alpha 2-globin gene: the same A----G replacement is present in the psi alpha l gene. The mutation must cause a considerable alpha-chain deficiency as is evidenced by the haematological data for five members with Hb H disease due to a compound heterozygosity for alpha-thalassaemia-1 (MED-II) and the newly discovered poly A mutation. Several members had additional beta-chain abnormalities (Hb S, Hb D-Los Angeles, beta-thalassaemia); the 11 persons with a Hb S heterozygosity and various alpha-globin gene defects (-alpha/alpha alpha; alpha T alpha/alpha alpha, - -/alpha alpha, -alpha/-alpha and - -/alpha T alpha) showed a decrease in the level of Hb S that was directly related to the severity of the alpha-chain deficiency.
Yüregir
G T
GT
Department of Biochemistry, Cukurova University, Adana, Turkey.
Aksoy
K
K
Cürük
M A
MA
Dikmen
N
N
Fei
Y J
YJ
Baysal
E
E
Huisman
T H
TH
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D004247:DNA / Q000737:chemistry; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D010375:Pedigree; D011061:Poly A / Q000235:genetics*; D013789:Thalassemia / Q000097:blood / Q000235:genetics*
D011061:Poly A; D005914:Globins; D004247:DNA