JAK2 V617 mutation triggers erythropoiesis and patients present with good hemoglobin level in idiopathic myelofibrosis [IMF]

To document the impact of JAK2 mutation on hemoglobin [Hb] level in patients with IMF. Thirty five patients were studied out of which 19 were JAK2 positive and 16 were JAK2 negative. Sample collection technique was purposive non-probability sampling. Variations were observed among the studied JAK2 positive and JAK2 negative patients regarding hemoglobin level. In JAK2 positive and negative patients mean hemoglobin level was 10.6g/dl and 8.6g/dl respectively [p=0.29]. Due to the better hemoglobin level, patients with JAK2 mutation have less transfusion requirements and are partially protected against severe anemias compared to patients with no mutation.

Comparison of serum creatine kinase estimation with short tandem repeats based linkage analysis in carriers and affected children of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy [DMD] is an X-linked recessive lethal, genetic disorder characterised by progressive weakness of skeletal muscles which is untreatable and transmitted to males by carrier females. Advances in laboratory techniques now focus direct mutational analysis as the most reliable and indirect analysis based on Short Tandem Repeats [STR] based linkage analysis as feasible, inexpensive, and efficient method for carrier detection and prenatal diagnosis. The objective of this study was to compare the sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and diagnostic efficiency of Serum Creatine Kinase [SCK] with Short Tandem Repeats [STR] based linkage analysis in carriers and affected children of Duchenne Muscular Dystrophy. The study was carried out from Dec 2006 to Dec 2007 in families having index clinical cases of DMD who were referred from different hospitals for evaluation/workup of DMD. SCK was done as a preliminary investigation in all index cases. The PCR assay with STR based linkage analysis with Intron 44, 45, 49 and 50 of DMD gene were performed in all families. Six families were informative with Intron 44 of DMD gene and one family was non-informative with all four intronic markers of DMD. SCK analyses were done in all the family members and compared with PCR analysis in informative families. SCK was not performed on Chorionic villous sample [CVS] done for prenatal diagnosis of DMD, and CVS and non-informative family members were excluded from the study. In carriers of DMD, the sensitivity and negative predictive value of SCK were 33.3%, and specificity and positive predictive were 100% with diagnostic efficiency of 50%. In affected cases of DMD the sensitivity and negative predictive value of SCK were 100%, and specificity and positive predictive were 91% and 88.8% respectively and diagnostic efficiency of 94.1%. The SCK is an excellent screening test for affected cases of DMD. For carrier identification we have to resort on PCR analysis so as to provide safer diagnostic tool for genetic counselling and prenatal diagnosis

Screening extended families for a genetic X-linked disorder, glucose 6 phosphate dehydrogenase deficiency

To test an alternative approach to population based program for identifying Glucose 6 Phosphate Dehydrogenase [G6PD] deficient Individuals in Pakistan where consanguineous marriage is common. This study was conducted at Armed Forces Institute of Pathology Rawalpindi and Pathology Department Government Lady Reading Hospital Peshawar. Five large families from Northern Pakistan, 03 with an index case of G6PD deficiency, 02 without such history [control] were screened for G6PD deficiency. All apparently healthy members of the families, both male and female of all ages, of the last three generations were included in the study. A commercial qualitative screening kit from Sigma Chemical Co. Ltd England was used for screening the individuals for G6PD deficiency. In the control families, no individual with G6PD deficiency was found among 101 individuals tested out of 159 living members. In the 03 families with an index case of G6PD deficiency 155 were tested out of 229 family member and 52 [33.5%] were found G6PD deficient. While in population screening out of 800 apparently healthy adult male subjects screened for G6PD deficiency, 47 [5.9%] were found glucose 6 phosphate dehydrogenase deficient. Testing extended families is feasible and highly cost effective way of screening for X- linked genetic disorder like Glucose 6 Phosphate Dehydrogenase deficiency in communities in which consanguineous marriage is common