Haptoglobin gene polymorphisms in sickle cell disease patients with different beta s-globin gene haplotypes

To investigate the prevalence of haptoglobin [Hp] gene alleles in Kuwaiti sickle cell disease [SCD] patients, who generally have a mild phenotype, and compare the pattern to Nigerian SCD patients whose SCD phenotype is more severe. Hp genotyping was carried out in a group of 82 and 54 SCD patients from Kuwait and Nigeria, respectively, and appropriate Hb AA controls. The Hp genotyping was done using a PCR technique followed by agarose gel electrophoresis. The frequency of the Hp-2 allele was 73.8% among Kuwaiti SCD patients, while the Hp-1 allele predominated among Nigerian patients [60.7%]. However, the differences were not significant [p > 0.05] when the allele distributions were compared between Kuwaiti SCD and their AA counterparts or between Nigerian SCD and their AA controls. There was no association of Hp-2 allele with frequent vaso-occlusive crisis among the Kuwaiti SCD patients. The distribution of Hp alleles appears to follow ethnic and geographical trends. Their role in the pathophysiology of pain crisis is not clear

Genotype-phenotype correlation among patients with dystrophinopathies

To correlate the site and size of dystrophin gene deletion with the clinical picture in patients with dystrophinopathies. The dystrophin gene is one of the largest known genes. More than half of the dystrophinopathy cases are associated with intrageneic deletions. The importance of the study arises from the fact that dystrophin cDNA probes provide a direct method of genetic diagnosis. This is the first study in an Arab population and only the second to use a three multiplex PCR method. Kuwait Medical Genetic Centre and Faculty of Medicine -Ain Shams University, Egypt Fifty-two patients with dystrophinopathies [50 with Duchenne muscular dystrophy [DMD] and 2 with Becker muscular dystrophy [BMD] from both Kuwait and Egypt were ascertained. Dystrophin gene deletions were detected using three multiplex reactions. DNA analysis showed that 71.4% of the patients had deletion of the dystrophin gene while 28.6% showed no deletion. 24.5% had two deleted exons while 14.3% had only one deleted exon. The most common deleted exons among the Kuwaiti patients were 81,45 and 48 while exons 19, 45, 48 and 51 were found more commonly deleted among the Egyptian patients. The onset of walking was not changed by the number of exons deleted except when five exons were deleted. However, delayed onset of walking was observed when exon 48,51 and 45 were deleted [r=0.6078, and p=0.110]. On the other hand, the average onset of weakness was neither correlated to the number of the exons deleted or to the deletion sites. Similar results were obtained regarding the average onset of wheel chair dependency. There was a slightly lower IQ with deletion of exons 48,45 and 12 but in general there is no correlation between the IQ and the site or the frequency of the deletion. Study of the intragenic deletions in 25 exons of the dystrophin gene using three different multiplex PCR sets revealed that 78%, 76% and 12% of DMD patients had deletion of each of the three sets separately. With all three sets together, the detection of deletion rate was increased to 86%. Fifty percent of the deleted exons were located in the distal hot spot, 8% in the proximal hot spot while 42% were scattered over both sides of the hot spot. No significant correlation was found between the size/site of the dystrophin deletions and the clinical severity. A multi centre larger study is recommended for a better understanding of the genotype-phenotype correlation

Genetic epidemiology of sickle cell anemia and B-thalassemia in Kuwait

Mutant beta[s] and alpha-beta- thalassemia alleles are found in polymorphic frequencies in the Arabian peninsula. The precise prevalence figures for Kuwait have, however, not been determined. Using PCR and allelepecific oligonucleotide hybridization techniques, we have characterized the alleles found among Kuwaiti SS, beta-thal major and beta-thal intermedia patients. alpha-Globin gene status was determined among the SS patients and their AS relatives. We have also attempted to identify the ethnic ancestries of the groups in which particular mutations were found. Most of our SS patients [75.9%] are homozygous for the Saudi Arabian/India haplotype, although a few with various combinations of the Benin and Bantu haplotypes are seen, alpha-thal determinants were found in 40% of the individuals studied; the -3.7 kb deletion [alpha-thal-2 trait] was the most common, accounting for 30.0% while non-deletional traits were found in -10%. Ten different beta-thal mutations have been identified so far among Kuwaitis. IVS-II-I[G - A] was the commonest in those of Saudi origin, the IVS-1 3 end 25 bp pair deletion was found only in those of Iranian descent. Only three mutations [the IVS-II-1 [G - A], IVS-I-1 [T-C] and codon 8 [-AA] were found in patients with thalassemia intermedia]. A knowledge of these mutations provides a basis for early and definitive diagnosis and promotes realistic genetic counseling and early institution of appropriate therapeutic measures in our patients

Interaction of the mosquitocidal crystal proteins from bacillus thuringiensis isreaelensis with phospholipid vesicles

The 125-130 KDa mosquitocidal proteins of the Bacillus thuringiensis israelensis delta-endotoxin were purified, activated in vitro and their interaction with phospholipid Iiposomes studied. The crystal proteins were found to cause a rapid increase in the light scattering of liposome suspensions, which reflects a morphological change in the lipid bilayer. When liposomes loaded with radioactive markers were incubated with activated crystal proteins a relatively rapid release of more than 60% of the trapped markers occurred. It is suggested that segments of the toxin molecules may become partitioned in the lipid bilayers to cause the formation of leakage pores