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1.  A catalase promoter variant rs1001179 is associated with visual acuity but not with primary angle closure glaucoma in Saudi patients 
BMC Medical Genetics  2013;14:84.
Background
To Investigate whether the g.4760C>T polymorphism in the promoter region of the catalase gene (CAT) is a risk factor for primary angle closure glaucoma (PACG) in the Saudi population.
Methods
138 unrelated PACG patients and 403 unrelated control subjects from Saudi Arabia were genotyped for a single nucleotide polymorphism (SNP; rs1001179; g.4760C>T) utilizing Taq-Man® assay. The association between different genotypes and various clinical indices important for PACG was also investigated.
Results
The distribution of different genotypes was comparable between both study groups. The genotype “C/C” was predominant among cafses; 94 (68.1%) and controls; 289 (71.7%). Heterozygous genotype “C/T”, was present in 41 (29.7%) of cases and 103 (25.6%) of controls, where the homozygous variant genotype was present in only 3 (2.2%) of cases and 11 (2.7%) of the controls. The distribution of variant allele was similar in both study groups (p= 0.568). Interestingly, there was a trend of association between the type of the variant (homozygous variant, heterozygous and wildtype genotype) and one important parameter for PACG, which is visual acuity. The visual acuity increase was; 0.62 (±0.74), 0.88 (±0.88) and 1.27 (±0.95) in patients carrying the “C/C”, “C/T” and “T/T” genotypes respectively, which was statistically significant in both ANOVA and pairwise individual T tests (p = 0.022, 0.031 and 0.039) when compared to controls.
Conclusions
This variant is possibly associated with visual acuity in PACG patients and thus had the potential to be used as a parameter for assessing PACG severity.
doi:10.1186/1471-2350-14-84
PMCID: PMC3765135  PMID: 23961996
Catalase; PACG; Saudi Arabia
2.  Molecular and neurological characterizations of three Saudi families with lipoid proteinosis 
BMC Medical Genetics  2011;12:31.
Background
Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood. It is caused by homozygous or compound heterozygous mutations in the ECM1 gene. The disease is largely uncharacterized in Arab population and the mutation(s) spectrum in the Arab population is largely unknown. We report the neurologic and neuroradiologic characteristics and ECM1 gene mutations of seven individuals with lipoid proteinosis (LP) from three unrelated consanguineous families.
Methods
Clinical, neurologic, and neuro-ophthalmologic examinations; skin histopathology; brain CT and MRI; and sequencing of the fullECM1 gene.
Results
All seven affected individuals had skin scarring and hoarseness from early childhood. The two children in Family 1 had worse skin involvement and worse hoarseness than affected children of Families 2 and 3. Both children in Family 1 were modestly mentally retarded, and one had typical calcifications of the amygdalae on CT scan. Affected individuals in Families 2 and 3 had no grossneurologic, neurodevelopmental, or neuroimaging abnormalities. Skin histopathology was compatible with LP in all three families. Sequencing the full coding region of ECM1 gene revealed two novel mutationsin Family 1 (c.1300-1301delAA) and Family 2 (p.Cys269Tyr) and in Family 3 a previously described 1163 bp deletion starting 34 bp into intron 8.
Conclusions
These individuals illustrate the neurologic spectrum of LP, including variable mental retardation, personality changes, and mesial temporal calcificationand imply that significant neurologic involvement may be somewhat less common than previously thought. The cause of neurologic abnormalities was not clear from either neuroimaging or from what is known about ECM1 function. The severity of dermatologic abnormalities and hoarseness generally correlated with neurologic abnormalities, with Family 1 being somewhat more affected in all spheres than the other two families. Nevertheless, phenotype-genotype correlation was not obvious, possibly because of difficulty quantifying the neurologic phenotype and because of genetic complexity.
doi:10.1186/1471-2350-12-31
PMCID: PMC3050790  PMID: 21349189
3.  A de novo marker chromosome derived from 9p in a patient with 9p partial duplication syndrome and autism features: genotype-phenotype correlation 
BMC Medical Genetics  2010;11:135.
Background
Previous studies focusing on candidate genes and chromosomal regions identified several copy number variations (CNVs) associated with increased risk of autism or autism spectrum disorders (ASD).
Case Presentation
We describe a 17-year-old girl with autism, severe mental retardation, epilepsy, and partial 9p duplication syndrome features in whom GTG-banded chromosome analysis revealed a female karyotype with a marker chromosome in 69% of analyzed metaphases. Array CGH analysis showed that the marker chromosome originated from 9p24.3 to 9p13.1 with a gain of 38.9 Mb. This mosaic 9p duplication was detected only in the proband and not in the parents, her four unaffected siblings, or 258 ethnic controls. Apart from the marker chromosome, no other copy number variations (CNVs) were detected in the patient or her family. Detailed analysis of the duplicated region revealed: i) an area extending from 9p22.3 to 9p22.2 that was previously identified as a critical region for the 9p duplication syndrome; ii) a region extending from 9p22.1 to 9p13.1 that was previously reported to be duplicated in a normal individual; and iii) a potential ASD locus extending from 9p24.3 to 9p23. The ASD candidate locus contained 34 genes that may contribute to the autistic features in this patient.
Conclusion
We identified a potential ASD locus (9p24.3 to 9p23) that may encompass gene(s) contributing to autism or ASD.
doi:10.1186/1471-2350-11-135
PMCID: PMC2946294  PMID: 20858261
4.  CADASIL in Arabs: clinical and genetic findings 
BMC Medical Genetics  2007;8:67.
Background
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs.
Methods
We studied three families from Saudi Arabia (Family A), Kuwait (Family B) and Yemen (Family C) with 19 individuals affected by CADASIL.
Results
The mean age of onset was 31 ± 6 and the clinical presentation included stroke in 68%, subcortical dementia in 17% and asymptomatic leukoariosis detected by MRI in 15%. Migraine and depression were frequently associated, 38% and 68% respectively. The mean age of death was 56 ± 11. All NOTCH3 exons were screened for mutations, which revealed the presence of previously reported mutations c.406C>T (p.Arg110>Cys) in two families (family A&B) and c.475C>T (p.Arg133>Cys) mutation in family C.
Conclusion
CADASIL occurs in Arabs, with clinical phenotype and genotype similar to that in other ethnic groups.
doi:10.1186/1471-2350-8-67
PMCID: PMC2190758  PMID: 17996090
5.  The interactive role of type 2 diabetes mellitus and E-selectin S128R mutation on susceptibility to coronary heart disease 
BMC Medical Genetics  2007;8:35.
Background
The role of gene-environment interactions as risk factors for coronary heart disease (CAD) remains largely undefined. Such interactions may involve gene mutations and disease conditions such as type 2 diabetes mellitus (DM2) predisposing individuals to acquiring the disease.
Methods
In the present study, we assessed the possible interactive effect of DM2 and E-selectin S128R polymorphism with respect to its predisposing individuals to CAD, using as a study model a population of 1,112 patients and 427 angiographed controls of Saudi origin. E-selectin genotyping was accomplished by polymerase chain reaction (PCR) amplification followed by PstI restriction enzyme digestion.
Results
The results show that DM2 is an independent risk factor for CAD. In the absence of DM2, the presence of the R mutant allele alone is not significantly associated with CAD (p = 0.431, OR 1.28). In contrast, in the presence of DM2 and the S allele, the likelihood of an individual acquiring CAD is significant (odds ratio = 5.44; p = < 0.001). This effect of DM2 becomes remarkably greater in the presence of the mutant 128R allele, as can be observed from the odds ratio of their interaction term (odds ratio = 6.11; p = < 0.001).
Conclusion
Our findings indicate therefore that the risk of acquiring CAD in patients with DM2 increases significantly in the presence of the 128R mutant allele of the E-selectin gene.
doi:10.1186/1471-2350-8-35
PMCID: PMC1933415  PMID: 17578587
6.  E-selectin S128R polymorphism and severe coronary artery disease in Arabs 
BMC Medical Genetics  2006;7:52.
Background
The E-selectin p. S128R (g. A561C) polymorphism has been associated with the presence of angiographic coronary artery disease (CAD) in some populations, but no data is currently available on its association with CAD in Arabs.
Methods
In the present study, we determined the potential relevance of the E-selectin S128R polymorphism for severe CAD and its associated risk factors among Arabs. We genotyped Saudi Arabs for this polymorphism by PCR, followed by restriction enzyme digestion.
Results
The polymorphism was determined in 556 angiographically confirmed severe CAD patients and 237 control subjects with no CAD as established angiographically (CON). Frequencies of the S/S, S/R and R/R genotypes were found as 81.1%, 16.6% and 2.3% in CAD patients and 87.8%, 11.8%, and 0.4% in CON subjects, respectively. The frequency of the mutant 128R allele was higher among CAD patients compared to CON group (11% vs. 6%; odds ratio = 1.76; 95% CI 1.14 – 2.72; p = .007), thus indicating a significant association of the 128R allele with CAD among our population. However, the stepwise logistic regression for the 128R allele and different CAD risk factors showed no significant association.
Conclusion
Among the Saudi population, The E-selectin p. S128R (g. A561C) polymorphism was associated with angiographic CAD in Univariate analysis, but lost its association in multivariate analysis.
doi:10.1186/1471-2350-7-52
PMCID: PMC1501005  PMID: 16756647
7.  T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking 
BMC Medical Genetics  2006;7:38.
Background
The association of the deletion in GSTT1 and GSTM1 genes with coronary artery disease (CAD) among smokers is controversial. In addition, no such investigation has previously been conducted among Arabs.
Methods
We genotyped 1054 CAD patients and 762 controls for GSTT1 and GSTM1 deletion by multiplex polymerase chain reaction. Both CAD and controls were Saudi Arabs.
Results
In the control group (n = 762), 82.3% had the T wild M wildgenotype, 9% had the Twild M null, 2.4% had the Tnull M wild and 6.3% had the Tnull M null genotype. Among the CAD group (n = 1054), 29.5% had the Twild M wild genotype, 26.6% (p < .001) had the Twild M null, 8.3% (p < .001) had the Tnull M wild and 35.6% (p < .001) had the Tnull M null genotype, indicating a significant association of the Twild M null, Tnull M wild and Tnull M null genotypes with CAD. Univariate analysis also showed that smoking, age, hypercholesterolemia and hypertriglyceridemia, diabetes mellitus, family history of CAD, hypertension and obesity are all associated with CAD, whereas gender and myocardial infarction are not. Binary logistic regression for smoking and genotypes indicated that only M null and Tnullare interacting with smoking. However, further subgroup analysis stratifying the data by smoking status suggested that genotype-smoking interactions have no effect on the development of CAD.
Conclusion
GSTT1 and GSTM1 null-genotypes are risk factor for CAD independent of genotype-smoking interaction.
doi:10.1186/1471-2350-7-38
PMCID: PMC1458325  PMID: 16620396
8.  The Glu27 genotypes of the Beta2-adrenergic receptor are predictors for severe coronary artery disease 
BMC Medical Genetics  2006;7:31.
Background
The role of the Beta2-adrenoceptor (beta2-AR) Gln27Glu polymorphism in the manifestation of cardiovascular diseases is still unclear.
Methods
In the present study, we evaluated the potential relevance of the c.79 C>G (p.Gln27Glu) polymorphism of this receptor gene for coronary artery disease (CAD) and its associated risk factors in Saudi Arabs. Genotyping was performed by PCR using the confronting two-pair primer (PCR-CTPP) method.
Results
In the general population group (BD) (n = 895), 68.5% were homozygous wild-type C/C, 28.3% were heterozygous C/G and 3.2% were homozygous mutant G/G. Among the CAD patients (n = 773), 50.6% were homozygous wild-type C/C, 43.6% were heterozygous C/G and 5.8% were homozygous mutant G/G, while in the angiographed control group (CON) (n = 528), 71.8% were C/C, 24.4% C/G and 3.8% G/G genotypes. These results indicate that both the C/G (p = < .001) and G/G (p = .005) genotypes are significantly associated with CAD, when compared to the CON group. In addition, C/G (p = < .001) and G/G (p = < .001) were significantly associated with CAD, when compared to the BD group. Furthermore, stepwise logistic regression showed that the genotype [C/G (p < .001) and G/G (p < .001)] increase the risk of CAD.
Conclusion
These results shows that the Gln27Glu genotypes (homo- or heterozygous) of the beta2-AR may be independent predictors of severe CAD.
doi:10.1186/1471-2350-7-31
PMCID: PMC1481543  PMID: 16573811

Results 1-8 (8)