Whole-Exome sequencing identifies GYS2 biallelic variants in individuals with suspected epilepsy.

Background: Adequate glucose supply is essential for brain function, therefore hypoglycemic states may lead to seizures. Since blood glucose supply for brain is buffered by liver glycogen, an impairment of liver glycogen synthesis by mutations in the liver glycogen synthase gene (GYS2) might result in a substantial neurological involvement. Here, we describe the phenotypes of affected siblings of two families harboring biallelic mutations in GYS2.

Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families.

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5-2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition.

Whole-Exome Sequencing of Pakistani Consanguineous Families Identified Pathogenic Variants in Genes of Intellectual Disability.

Intellectual disability (ID) is a condition of significant limitation of cognitive functioning and adaptive behavior, with 50% of etiology attributed to genetic predisposition. We recruited two consanguineous Pakistani families manifesting severe ID and developmental delay. The probands were subjected to whole exome sequencing (WES) and variants were further prioritized based on population frequency, predicted pathogenicity and functional relevance.

Demographic and Clinical Determinants of Tuberculosis and TB Recurrence: A Double-Edged Retrospective Study from Pakistan.

Objective: TB recurrence is the second episode of TB after initial treatment bringing about an additional 7% load in TB burden intensified by 17.7% of multidrug-resistant recurrent cases. It is necessary to curb recurrence so that attempts to deal with active disease can be made more effective.

Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine-mapping in the MHC and genomewide.

Because transethnic analysis may facilitate prioritization of causal genetic variants, we performed a genomewide association study (GWAS) of psoriasis in South Asians (SAS), consisting of 2,590 cases and 1,720 controls. Comparison with our existing European-origin (EUR) GWAS showed that effect sizes of known psoriasis signals were highly correlated in SAS and EUR (Spearman ρ = 0.78; < 2 × 10).

Association study of Apolipoprotein A5 gene (APOA5 gene) variant with the metabolic syndrome in local Pakistani population.

Objective: To explore the association of rs662799 variants of Apolipoprotein A5 gene with metabolic syndrome in Pakistani population.

Methods: The case-control study was conducted at Pakistan Institute of Medical Sciences, Islamabad, Pakistan from 2014 to2016, and comprised subjects enrolled from the out-patient clinics. Groups were formed on the basis of preliminary screening for risk factors like obesity, insulin resistance, hypertension, dyslipidemia and fasting blood glucose levels.

Exome sequencing circumvents missing clinical data and identifies a BSCL2 mutation in congenital lipodystrophy.

Background: Exome sequencing has become more and more affordable and the technique has emerged as an important diagnostic tool for monogenic disorders at early stages of investigations, in particular when clinical information is limited or unspecific as well as in cases of genetic heterogeneity.

Methods: We identified a consanguineous Pakistani family segregating an autosomal recessive phenotype characterized by muscular hypertrophy, mild mental retardation and skeletal abnormalities. The available clinical information was incomplete and we applied whole exome sequencing in an affected family member for the identification of candidate gene variants.