Denovo variants in POGZ and YY1 genes: The novel mega players for neurodevelopmental syndromes in two unrelated consanguineous families.

Novel denovo variants of exome sequences are major cause of pathogenic neurodevelopmental disorders with a dominant genetic mechanism that emphasize their heterogeneity and complex phenotypes. White Sutton syndrome and Gabriele-de-Vries syndrome are congenital neuro-impairments with overlap of severe intellectual disability, microcephaly, convulsions, seizures, delayed development, dysmorphism of faces, retinal diseases, movement disorders and autistic traits. POGZ gene codes for pogo transposable element-derived zinc-finger protein and YY1 gene regulates transcription, chromatin, and RNA-binding proteins that have been associated with White Sutton and Gabriele-de-Vries syndromes, in recent data.

Genetic Heterogeneity in Four Probands Reveals , , and Related Neurodevelopmental Disorders.

: Neurodevelopmental disorders of genetic etiology are a highly diverse set of congenital recurrent complications triggered by irregularities in the basic tenets of brain development. : We present whole exome sequencing analysis and expression characteristics of the probands from four unrelated Pakistani consanguineous families with facial dysmorphism, neurodevelopmental, ophthalmic, auditory, verbal, psychiatric, behavioral, dental, and skeletal manifestations otherwise unexplained by clinical spectrum. : Whole exome sequencing identifies a novel, bi-allelic, missense variant in the gene [NM_152419.

Novel and known minor alleles of CNTNAP2 gene variants are associated with comorbidity of intellectual disability and epilepsy phenotypes: a case-control association study reveals potential biomarkers.

Background: Neurodevelopmental disorders are heterogeneous due to underlying multiple shared genetic pathways and risk factors. Intellectual disability, epilepsy and autism spectrum disorder phenotypes overlap which indicates the diverse effects of common genes. Recent studies suggested the probable contribution of CNTNAP2 gene polymorphisms to the comorbidity of these neurological conditions.

Genome-wide CNV analysis uncovers novel pathogenic regions in cohort of five multiplex families with neurodevelopmental disorders.

Structural reorganization of chromosomes by genomic duplications and/or deletions are known as copy number variations (CNVs). Pathogenic and disease susceptible CNVs alter gene dosage and its phenotypic expression that often leads to human genetic diseases including Neurological disorders. CNVs affecting same common genes in multiple neurodevelopmental disorders can better explain the shared clinical and genetic aetiology across brain diseases.

Association of 11 variants of the dopaminergic and cognitive pathways genes with major depression, schizophrenia and bipolar disorder in the Pakistani population.

: The dopaminergic pathways control neural signals that modulate mood and behaviour along and have a vital role in the aetiology of major depression (MDD), schizophrenia (SHZ) and bipolar disorder (BD). Genome-wide association studies (GWAS) have reported several dopaminergic and cognitive pathway genes association with these disorders however, no such comprehensive data was available regarding the Pakistani population.: The present study was conducted to analyse the 11 genetic variants of dopaminergic and cognitive system genes in MDD, SHZ, and BD in the Pakistani population.

Microcephaly, Short Stature, Intellectual Disability, Speech Absence and Cataract Are Associated with Novel Bi-Allelic Missense Variant in Gene: A Seckel Syndrome Case Report.

The gene encodes centriole biogenesis, replication, symmetry and cohesion, basal body organization and has recently been associated with the appearance of microcephaly syndromes. -related neurological defects including microcephaly, intellectual disability, congenital dwarfism, ophthalmic manifestations, and epilepsy are mainly due to abnormal brain development pathways and loss-of-function protein mutations. We present a consanguineous Pakistani family clinically suspected of Seckel syndrome with severe microcephaly, severe intellectual disability, short stature, absence of speech, pointed nose, narrow face and bilateral cataract in two siblings residing in the suburbs of Islamabad.

Contributing risk factors of common psychiatric disorders in the Pakistani population.

With an increasing incidence of psychiatric disorders worldwide, there is a need for a better understanding of the population-specific contributing risk factors that are associated with common psychiatric conditions. This study aimed to assess the correlation between socioeconomic, environmental and clinical features associated with major depression (MDD n = 479), bipolar disorder (BD n = 222) and schizophrenia (SHZ n = 146), in the Pakistani population. Multinomial logistic regression and Pearson's correlation were applied to assess the association and correlation between demographic, socioeconomic, environmental, and clinical features of MDD, BD and SHZ.

A common missense variant rs874881 of PADI4 gene and rheumatoid arthritis: Genetic association study and in-silico analysis.

The peptidylarginine-deiminase 4 (PADI4) is involved in the post-translational catalytic conversion of arginine into citrulline. The autoantibodies including anti-citrullinated protein antibodies (ACPAs) produced in response to hypercitrullinated proteins are a hallmark of rheumatoid arthritis (RA) autoimmunity. Therefore, the role of a missense variant rs874881 (Gly112Ala) of PADI4 in RA susceptibility was analyzed, along with in-silico analysis of structural and functional impacts of this substitution.

novel frameshift variant p.(Ser887Profs*64) exhibits clinical heterogeneity in a Pakistani family with hereditary sensory and autonomic neuropathy type IIC.

Hereditary sensory and autonomic neuropathies (HSANs) are rare heterogeneous group of neurological disorders caused by peripheral nerve deterioration. The HSANs sub-clinical classes have clinical and genetic overlap which often lead to misdiagnosis. In the present study a Pakistani family with five affected members suffering from severe neuropathy were genetically analyzed to identify the disease causative element in the family.

Role of 19 SNPs in 10 genes with type 2 diabetes in the Pakistani population.

Meta-GWAS report numerous variants associated with type 2 diabetes (T2D), however, for diabetic retinopathy (DR) no loci achieved genome-wide significance. There are limited candidate gene analyses for T2D and/or DR reported from the Pakistani population. Therefore, the current study was designed to evaluate the genetic association of 10 loci with T2D, non-proliferative DR (NPDR), and proliferative DR (PDR).

De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder.

Purpose: Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene (ZNF292).

Methods: We ascertained a cohort of 28 families with ID due to putatively pathogenic ZNF292 variants that were identified via targeted and exome sequencing.

Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features.

Cargo transport along the cytoplasmic microtubular network is essential for neuronal function, and cytoplasmic dynein-1 is an established molecular motor that is critical for neurogenesis and homeostasis. We performed whole-exome sequencing, homozygosity mapping, and chromosomal microarray studies in five individuals from three independent pedigrees and identified likely-pathogenic variants in DYNC1I2 (Dynein Cytoplasmic 1 Intermediate Chain 2), encoding a component of the cytoplasmic dynein 1 complex. In a consanguineous Pakistani family with three affected individuals presenting with microcephaly, severe intellectual disability, simplification of cerebral gyration, corpus callosum hypoplasia, and dysmorphic facial features, we identified a homozygous splice donor site variant (GenBank: NM_001378.

A de novo microdeletion in NRXN1 in a Dutch patient with mild intellectual disability, microcephaly and gonadal dysgenesis.

This report is regarding a Dutch female with microcephaly, mild intellectual disability (ID), gonadal dysgenesis and dysmorphic facial features with synophrys. Upon genotyping, an ~455 kb de novo deletion encompassing the first exon of NRXN1 was found. Bidirectional sequencing of the coding exons of the NRXN1 alpha isoform was subsequently performed to investigate the possibility of a pathogenic mutation on the other allele, but we could not find any other mutation.

Exome sequencing identifies three novel candidate genes implicated in intellectual disability.

Intellectual disability (ID) is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-syndromic Pakistani families.

A complex microcephaly syndrome in a Pakistani family associated with a novel missense mutation in RBBP8 and a heterozygous deletion in NRXN1.

We report on a consanguineous Pakistani family with a severe congenital microcephaly syndrome resembling the Seckel syndrome and Jawad syndrome. The affected individuals in this family were born to consanguineous parents of whom the mother presented with mild intellectual disability (ID), epilepsy and diabetes mellitus. The two living affected brothers presented with microcephaly, white matter disease of the brain, hyponychia, dysmorphic facial features with synophrys, epilepsy, diabetes mellitus and ID.

A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet-Biedl syndrome in a Pakistani family.

Bardet-Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet-Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet-Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet-Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease.