Frequency of Gc-globin promoter 158 [C>T] XmnI polymorphism in patients with homozygous/compound heterozygous beta thalassaemia

BACKGROUND: Response to hydroxyurea therapy in homozygous or compound heterozygous beta thalassaemia [BT] has been reported as more favourable in the presence of XmnI polymorphism. The prevalence of XmnI polymorphism may vary with BT phenotypes and genotypes, and differs geographically in distribution. Prevalence of XmnI polymorphism is not known in northern Pakistan. Objective: To determine the frequency of Gc-globin promoter 158 [C>T] XmnI polymorphism [XmnI polymorphism] in patients with homozygous or compound heterozygous beta thalassaemia. MATERIALS: Polymerase chain reaction [PCR] for common beta thalassaemia mutations and Gc-globin promoter 158 [C>T] XmnI polymorphism was performed on 107 blood samples of transfusion dependent beta thalassaemia [BT] patients in Pakistan. One hundred samples of unrelated BT traits and 94 samples of healthy subjects as controls were also analysed for BT mutations and XmnI polymorphism. Results: Out of 301 DNA samples, XmnI polymorphism was detected in 71[24%]; in normal controls, XmnI polymorphism was detected in 34/94 [36%] subjects; while in homozygous/compound heterozygous BT, it was detected in 14/107[13%] patients [Fisher's exact test, p =. 0002]. In heterozygous BT group, XmnI polymorphism was detected in 23/100 subjects [Fisher's exact test, p =. 03 with normal controls, and p =. 049 with homozygous/compound heterozygous BT]. The most common BT genotype was Frame Shift [Fr] 8–9/Fr 8–9, and none of the patients with this genotype had XmnI polymorphism. The second most common genotype was IVSI-5/IVSI-5; 4/26 [15%]. Cases with this genotype had XmnI polymorphism. Conclusion: XmnI polymorphism in homozygous/compound heterozygous BT group is 13%. The most common genotype associated with XmnI polymorphism was IVSI-5/IVSI-5

Silent mutations of thalassaemia - a diagnostic dilemma

A case of thalassaemia intermedia resulting from compound heterozygosity between Fr8-9 and Cap+1 mutation is presented. Patient's father had undergone premarital thalassaemia screening and was declared free of thalassaemia due to normal HbA[2] levels. We aim to discuss the clinico-haemtological features and diagnostic approach for Cap+1 mutation in carrier as well as compound heterozygous state with a beta[0] mutation

JAK2 mutation and myeloproliferative disorders in Pakis

To study the haematological features and JAK2 mutation in Pakistani patients of myeloproliferative disorders. Descriptive cross sectional. Department of Heamatology, Armed Forces Institute of Pathology, Rawalpindi from Jan 2004 to Jan 2007. Forty seven consecutive patients of myeloproliferative disorders [MPD] diagnosed by the conventional haematological criteria were included in the study. The patients on treatment were excluded. Age, sex, splenic enlargement, blood complete counts and bone marrow examination findings were recorded. All patients were screened for G-T Point mutation [V617F] in the JAK2 gene on chromosome 9 by an allele specific PCR Out of the 47 MPD patients, 17 [36%] had polycythaemia rubra vera [PRV], 7 [15%] had essential thrombocythaemia [ET] and 18 [38%] had idiopathic myelofibrosis [MF]. JAK2 positive was seen in 37/47 [79%] patients including 17/17 [100%] in PRV, 4/7 [57%] in ET and 13/18 [72%] in IMF. MPDs are an important group of haematology disorders in Pakistan. Vast majority of these disorders [79%] showed mutation in the JAK2 gene. JAK2 mutation analysis is especially useful in the diagnosis of polycythaemia vera where it was found in 100% of the cases