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Mohammed Shakil Akhtar

Other affiliations: King Fahd University Hospital
Bio: Mohammed Shakil Akhtar is an academic researcher from University of Dammam. The author has contributed to research in topics: Population & Exome sequencing. The author has an hindex of 6, co-authored 11 publications receiving 138 citations. Previous affiliations of Mohammed Shakil Akhtar include King Fahd University Hospital.

Papers
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Journal ArticleDOI
TL;DR: The high frequency of α- and β-thal in the Eastern Province of Saudi Arabia and their coinheritance, necessitates the inclusion ofα-thal testing in the current pre marital testing program to highlight the risk to the offspring of affected individuals.
Abstract: Both α- and β-thalassemia (α- and β-thal) are highly prevalent in the population of the Al-Qatif and Al-Ahsa regions in the Eastern Province of Saudi Arabia. This study provides a more precise picture of the α-thal mutations prevalent in 104 transfusion-dependent β-thal patients in the Eastern Province. Detection of α-thal mutations was carried out using the α-globin StripAssay kit. A total of 12 α-thal mutations (21 genotypes) were identified in 33.7% of the chromosomes (46 patients). The heterozygous and homozygous -α(3.7) (α(+)) deletion mutations were the most prevalent in the β-thal patients (21.7%). We identified three α(0) deletions [- -(MED), - -(FIL) and -(α)20.5] that have not been previously reported for the population of Saudi Arabia. The seven point mutations identified in the β-thal patients were: codon 14 [TGG>TAG (α1)], codon 59 [GGC>GAC (α1)] (Hb Adana), polyadenylation signal site (polyA1) [AATAAA>AATAAG (α2)], codon 142 [TAA>TCA (α2)] (Hb Koya Dora), codon 59 [GGC>GAC (α2)] (Hb Adana), initiation codon [ATG>ACG (α2)] and the ααα(anti 3.7) gene triplication. The Hb Koya Dora mutation occurred at the highest frequency (15.38%). Comparison of the clinical phenotype of β-thal patients, with and without an α-thal mutation, showed that patients with β-thal alone had a significantly elevated level of alanine transaminase (ALT) (mean 72.5 IU/L) and aspartate transaminase (AST) (mean 71.8 IU/L) (p <0.005). In addition, the β-thal patients without an α-thal mutation had a higher percentage of osteoporosis (16.6%), fractures (12.5%), and splenectomies (58.3%). This confirms previous data that the co-inheritance of α-thal in β-thal patients results in the amelioration of the clinical phenotype of β-thal patients. Moreover, the high frequency of α- and β-thal in the Eastern Province of Saudi Arabia and their coinheritance, necessitates the inclusion of α-thal testing in the current pre marital testing program to highlight the risk to the offspring of affected individuals.

33 citations

Journal ArticleDOI
25 May 2020-Heart
TL;DR: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.
Abstract: Objective Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM. Methods TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls. Results Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15–69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%). Conclusion TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.

22 citations

Journal ArticleDOI
TL;DR: The rs5882 polymorphism (CETP) showed a significant association with CAD and therefore could be a promising marker for CAD risk estimation while the rs708272 polymorphism had a protective effect from CAD.
Abstract: Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Many genetic and environmental risk factors including atherogenic dyslipidemia contribute towards the development of CAD. Functionally relevant mutations in the dyslipidemia-related genes and enzymes involved in the reverse cholesterol transport system are associated with CAD and contribute to increased susceptibility of myocardial infarction (MI). Blood samples from 990 angiographically confirmed Saudi CAD patients with at least one event of myocardial infarction were collected between 2012 and 2014. A total of 618 Saudi controls with no history or family history of CAD participated in the study. Four polymorphisms, rs2230806, rs2066715 (ABCA1), rs5882, and rs708272 (CETP), were genotyped using TaqMan Assay. CETP rs5882 (OR = 1.45, P < 0.005) and ABCA1 rs2230806 (OR = 1.42, P = 0.017) polymorphisms were associated with increased risk of CAD. However, rs708272 polymorphism showed protective effect (B1 vs. B2: OR = 0.80, P = 0.003 and B2B2 vs. B1B1: OR = 0.68, P = 0.012) while the ABCA1 variant rs2066715 was not associated. This study is the first to report the association of these polymorphisms with CAD in the population of the Eastern Province of Saudi Arabia. The rs5882 polymorphism (CETP) showed a significant association and therefore could be a promising marker for CAD risk estimation while the rs708272 polymorphism had a protective effect from CAD.

19 citations

Journal ArticleDOI
TL;DR: HbA2 has a measure of unreliability in the diagnosis of β-thalassemia carriers, and can be incorrectly diagnosed as carriers.
Abstract: Introduction: Detection of β-thalassemia trait or carriers (β-TT) depends significantly on an increase in Hemoglobin A2 (HbA2) levels, which is found at low levels (<3%) in normal healthy individua...

19 citations


Cited by
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Sonia Shah1, Albert Henry2, Carolina Roselli3, Honghuang Lin4  +164 moreInstitutions (58)
TL;DR: Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension.
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

326 citations

Journal ArticleDOI
TL;DR: This research presents a novel probabilistic approach that allows us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals.
Abstract: Background: The genetic basis of left ventricular (LV) image-derived phenotypes, which play a vital role in the diagnosis, management, and risk stratification of cardiovascular diseases, is unclear...

121 citations

Journal ArticleDOI
TL;DR: It is concluded that CEGMR will continue to play a pivotal role in advances in the field of genomics and research in this area is facing a number of challenges including generating high quality control data from Saudi population and policies for using these data need to comply with the international set up.
Abstract: The biomedical research sector in Saudi Arabia has recently received special attention from the government, which is currently supporting research aimed at improving the understanding and treatment of common diseases afflicting Saudi Arabian society. To build capacity for research and training, a number of centres of excellence were established in different areas of the country. Among these, is the Centre of Excellence in Genomic Medicine Research (CEGMR) at King Abdulaziz University, Jeddah, with its internationally ranked and highly productive team performing translational research in the area of individualized medicine. Here, we present a panorama of the recent trends in different areas of biomedical research in Saudi Arabia drawing from our vision of where genomics will have maximal impact in the Kingdom of Saudi Arabia. We describe advances in a number of research areas including; congenital malformations, infertility, consanguinity and pre-implantation genetic diagnosis, cancer and genomic classifications in Saudi Arabia, epigenetic explanations of idiopathic disease, and pharmacogenomics and personalized medicine. We conclude that CEGMR will continue to play a pivotal role in advances in the field of genomics and research in this area is facing a number of challenges including generating high quality control data from Saudi population and policies for using these data need to comply with the international set up.

63 citations

Journal ArticleDOI
TL;DR: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD, and male sex and LVSD are independent predictors of outcomes.
Abstract: Background: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. Methods...

51 citations

Journal ArticleDOI
TL;DR: The authors focus on genetics of dilated cardiomyopathy and provide a roadmap for implementing genomic information into future patient management.

46 citations