Genetic position of Bahrain natives among wider Middle East populations according to Alu insertion polymorphisms.

BACKGROUND: The genetic differentiation of Bahrain natives is unclear because of the absence of adequate genetic studies. AIM: Eight Alu insertion polymorphisms have been analysed in Bahrainis and southern Iranians to examine the origins of Bahrainis and to determine their genetic position among wider Middle East populations. SUBJECTS AND METHODS: Two representative samples of 97 Bahrainis and 65 southern Iranians have been determined. Genetic relationships among populations have been estimated by a principal component plot based on the R-matrix software. Mantel tests have been used to check the statistical significance of correlation between genetic and geographic distances. RESULTS: The results show that Bahrainis are in an intermediate genetic position between Emirians and Southern Iranians. Although a general significant correlation between genetic and geographic distances was found between the 16 populations included in the analysis, a lack of this correlation may occur in some particular situations such as the case of populations from southern Iran, United Arab Emirates (UAE) and Bahrain, separated by the Persian Gulf. CONCLUSION: The results support the idea that Bahrainis ancestors were mainly emigrants from Arabia and Iran. In addition the results show that the Iranian component may reach 69.2% of the current genetic pool of Bahrainis.

The Arabic allele: a single base pair substitution activates a 10-base downstream cryptic splice acceptor site in exon 12 of LDLR and severely decreases LDLR expression in two unrelated Arab families with familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a monogenic autosomal dominant disorder caused by defects in LDLR. Few reports describe FH mutations among Arabs. We describe a mutation in LDLR of two unrelated Arab families. We investigated 19 patients using DNA sequencing, RFLP, and real-time (RT) PCR. DNA sequencing showed a base pair substitution (c.1706-2 A>T) in the splice acceptor site of LDLR intron 11. Our results were confirmed by RFLP on 2% agarose gel. In silico analysis predicted a new cryptic splice site downstream of the original position generating a 10-base deletion from the beginning of exon 12; (c.1706-1715del.ATCTCCTCAG). cDNA sequencing of exon 12 confirmed the computational analysis. The deletion was visualized on 4% agarose gel. The deletion generates a frameshift and a premature termination codon (c.1991-1993; p.(Asp569Valfs*93). RT-PCR revealed that LDLR mRNA is 9.3%±6.5 and 17.9%±8.0 for FH homozygote and heterozygote individuals respectively, compared to a healthy family control. We predict a class II LDLR mutation that leads to a truncated receptor missing exons 14-18. We called this mutation "the Arabic allele". We expect a significant contribution of this mutation to the prevalence of FH among Arabs. Also, we propose that the severe down regulation of LDLR mRNA expression is due to nonsense-mediated-decay.

Mutations in the RNA granule component TDRD7 cause cataract and glaucoma.

The precise transcriptional regulation of gene expression is essential for vertebrate development, but the role of posttranscriptional regulatory mechanisms is less clear. Cytoplasmic RNA granules (RGs) function in the posttranscriptional control of gene expression, but the extent of RG involvement in organogenesis is unknown. We describe two human cases of pediatric cataract with loss-of-function mutations in TDRD7 and demonstrate that Tdrd7 nullizygosity in mouse causes cataracts, as well as glaucoma and an arrest in spermatogenesis. TDRD7 is a Tudor domain RNA binding protein that is expressed in lens fiber cells in distinct TDRD7-RGs that interact with STAU1-ribonucleoproteins (RNPs). TDRD7 coimmunoprecipitates with specific lens messenger RNAs (mRNAs) and is required for the posttranscriptional control of mRNAs that are critical to normal lens development and to RG function. These findings demonstrate a role for RGs in vertebrate organogenesis.

Germline mutation in the von Hippel-Lindau gene in Kuwait: a clinical and molecular study.

OBJECTIVES: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL) family in Kuwait with Arabian and Persian genetic admixture. MATERIALS AND METHOD: Polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) and direct sequencing of the PCR amplicons, that showed clear band shift, were used to screen the VHL gene in the index patient, 20 members of her family and 55 healthy controls of matching ethnicity. RESULT: The clinical history of all patients revealed multiple hemangioblastomas in various organs without pheochromocytomas. SSCP showed a clear band shift in 2 PCR amplicons, which were then sequenced. One was in the promoter region revealing a polymorphic site (A-123G) found as heterozygous in 40% of the healthy control subjects of the same ethnicity. The second band shift was in exon 2 seen in all clinically diagnosed VHL cases but not in the healthy members of the family or the screened healthy population. Direct sequencing revealed it was a heterozygous missense mutation G564T (Trp117Cys). Tracking the mutation in the family pedigree showed its origin from the Persian side. CONCLUSION: This is a second missense G564T mutation in another VHL patient from Kuwait that will help expand our knowledge of the VHL gene mutation spectrum in this region of the world.

Effects of cigarette smoking on hematological parameters and von Willebrand factor functional activity levels in asymptomatic male and female Arab smokers.

OBJECTIVES: This study aimed at determining the effects of cigarette smoking based on gender, on several hematological parameters and von Willebrand factor protein in the asymptomatic Arab population of Kuwait. SUBJECTS AND METHODS: Ninety-two subjects participated in this study: 55 males (31 smokers and 24 nonsmokers) and 37 females (18 smokers and 19 nonsmokers). Complete blood count results were obtained using Beckman Coulter Hematology Analyzer. Von Willebrand factor functional activity was determined using an enzyme-linked immunoassay-based test in which anti-von Willebrand factor IgG monoclonal antibody was used that recognizes a functional epitope of the protein. The coagulation profile was obtained using ACL 9000 coagulation analyzer. RESULTS: Male smokers had significantly higher levels of white blood cell count (p = 0.03) and von Willebrand factor protein levels (p = 0.029), and a significantly shorter thrombin time (p = 0.019) than nonsmokers. Smoking did not appear to affect any of the parameters analyzed in females as no significant difference was found between smokers and nonsmokers (p > 0.05). CONCLUSION: Our results showed that smoking affected white blood cell count and von Willebrand factor levels in males and not in females, and as such could be potential markers for smoking-induced endothelial damage in asymptomatic Arab male smokers.

Validity assessment of nine discriminant functions used for the differentiation between iron deficiency anemia and thalassemia minor.

Iron deficiency anemia (IDA) and thalassemia minor are two of the most common causes of microcytic anemias worldwide. Because of similar red blood cell count parameters and blood picture, it was imperative to develop other measures that would differentially and correctly diagnose these two anemias. Several mathematical formulas and simple RBC indices have been introduced as simple, fast and inexpensive means of providing differential diagnosis for IDA and thalassemia minor. The Objective of this study was to apply and compare nine well-documented discriminant functions on a population of 153 confirmed cases of microcytic anemias (IDA n = 56, beta-thalassemia minor n = 47 and alpha-thalassemia n = 50) and to measure validity using Youden's Index. The results show that England and Fraser (E & F) Index had the highest Youden's Index value (98.2) in correctly differentiating between IDA and alpha- and beta-thalassemia minor, while Shine and Lal Index was found ineffective in differentiating between microcytic anemias in our population. E & F Index showed with great sensitivity and specificity to be the best discriminant function to differentiate between IDA and thalassemia minor cases.

Comparison of erythrocyte sedimentation rate measurement by the automated SEDIsystem and conventional Westergren method using the Bland and Altman statistical method.

OBJECTIVES: To compare the performance of SEDIsystem(TM), a fully automated analyzer for the measurement of the erythrocyte sedimentation rate (ESR), with the manual Westergren method. MATERIALS AND METHODS: Both methods were applied to 150 randomly selected subjects. The linear regression and Bland and Altman data analysis methods were used to measure the agreement between the automated and manual methods. RESULTS: The regression analysis showed a good correlation between the two methods (r=0.91). The Bland and Altman data analysis showed no systematic bias (95% confidence interval for mean difference); however, limits of agreement were between 11.52 and -37.88. This indicates that ESR values measured by the SEDIsystem may be 11.52 mm/h above or 37.88 mm/h below the reference method. A greater scatter of data was also observed with abnormally high (>25 mm/h) ESR results (mean of difference=-21.4 and limits of agreement=-45.2 and 2.26) compared with normal (<25 mm/h) readings (mean of difference=-3.9 and limits of agreement=-13.5 and 5.7). CONCLUSION: The Bland and Altman statistical analysis showed a wide degree of scatter between results obtained by the two ESR techniques that was not clearly demonstrated using the linear regression analysis. The automated system was found to underestimate ESR with the Bland and Altman statistical analysis, and therefore a correction factor is recommended.