title: Spectrum of α-thalassemia mutations in transfusion-dependent β-thalassemia patients from the Eastern Province of Saudi Arabia.
abstract: Both α- and β-thalassemia (α- and β-thal) are highly prevalent in the population of the Al-Qatif and Al-Ahsa regions in the Eastern Province of Saudi Arabia. This study provides a more precise picture of the α-thal mutations prevalent in 104 transfusion-dependent β-thal patients in the Eastern Province. Detection of α-thal mutations was carried out using the α-globin StripAssay kit. A total of 12 α-thal mutations (21 genotypes) were identified in 33.7% of the chromosomes (46 patients). The heterozygous and homozygous -α(3.7) (α(+)) deletion mutations were the most prevalent in the β-thal patients (21.7%). We identified three α(0) deletions [- -(MED), - -(FIL) and -(α)20.5] that have not been previously reported for the population of Saudi Arabia. The seven point mutations identified in the β-thal patients were: codon 14 [TGG>TAG (α1)], codon 59 [GGC>GAC (α1)] (Hb Adana), polyadenylation signal site (polyA1) [AATAAA>AATAAG (α2)], codon 142 [TAA>TCA (α2)] (Hb Koya Dora), codon 59 [GGC>GAC (α2)] (Hb Adana), initiation codon [ATG>ACG (α2)] and the ααα(anti 3.7) gene triplication. The Hb Koya Dora mutation occurred at the highest frequency (15.38%). Comparison of the clinical phenotype of β-thal patients, with and without an α-thal mutation, showed that patients with β-thal alone had a significantly elevated level of alanine transaminase (ALT) (mean 72.5 IU/L) and aspartate transaminase (AST) (mean 71.8 IU/L) (p <0.005). In addition, the β-thal patients without an α-thal mutation had a higher percentage of osteoporosis (16.6%), fractures (12.5%), and splenectomies (58.3%). This confirms previous data that the co-inheritance of α-thal in β-thal patients results in the amelioration of the clinical phenotype of β-thal patients. Moreover, the high frequency of α- and β-thal in the Eastern Province of Saudi Arabia and their coinheritance, necessitates the inclusion of α-thal testing in the current pre marital testing program to highlight the risk to the offspring of affected individuals.
authors.affiliation: Department of Biochemistry, University of Dammam, Dammam 31441, Saudi Arabia. makhtar@ud.edu.sa
authors.forename: Mohammed Shakil
authors.initials: MS
authors.lastname: Akhtar
authors.forename: Fuad
authors.initials: F
authors.lastname: Qaw
authors.forename: J Francis
authors.initials: JF
authors.lastname: Borgio
authors.forename: Waleed
authors.initials: W
authors.lastname: Albuali
authors.forename: Ahmed
authors.initials: A
authors.lastname: Suliman
authors.forename: Zaki
authors.initials: Z
authors.lastname: Nasserullah
authors.forename: Sana
authors.initials: S
authors.lastname: Al-Jarrash
authors.forename: Amein
authors.initials: A
authors.lastname: Al-Ali
mesh_terms: D001803:Blood Transfusion; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D012529:Saudi Arabia / Q000453:epidemiology; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000453:epidemiology / Q000235:genetics*; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy
chemical_list: D055542:alpha-Globins