A Novel Ornithine Aminotransferase Splice Site Mutation Causes Vitamin B6-Responsive Gyrate Atrophy.

Purpose: Gyrate atrophy of the choroid and retina (GACR) is a rare congenital disorder and mutations in the ornithine aminotransferase (OAT) gene has been specified as the underlying cause. Patients show a high level of ornithine in body fluids which may be controlled by low protein diets. Pyridoxine (vitamin B6) supplementation may also be effective, however, most patients appear to be nonresponsive to this modality of treatment.

Negative association between anterior insula activation and resilience during sustained attention: an fMRI twin study.

Background: While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations.

Methods: The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure.

Associations between mental wellbeing and fMRI neural bases underlying responses to positive emotion in a twin sample.

Background: Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment.

Methods: We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task.

Wellbeing and brain structure: A comprehensive phenotypic and genetic study of image-derived phenotypes in the UK Biobank.

Wellbeing, an important component of mental health, is influenced by genetic and environmental factors. Previous association studies between brain structure and wellbeing have typically focused on volumetric measures and employed small cohorts. Using the UK Biobank Resource, we explored the relationships between wellbeing and brain morphometrics (volume, thickness and surface area) at both phenotypic and genetic levels.

Phenotypic and genetic analysis of a wellbeing factor score in the UK Biobank and the impact of childhood maltreatment and psychiatric illness.

Wellbeing is an important aspect of mental health that is moderately heritable. Specific wellbeing-related variants have been identified via GWAS meta-analysis of individual questionnaire items. However, a multi-item within-subject index score has potential to capture greater heritability, enabling improved delineation of genetic and phenotypic relationships across traits and exposures that are not possible on aggregate-data.

Interleukine-22 gene variants are associated with susceptibility to visceral leishmaniasis.

Visceral leishmaniasis (VL) is an infectious disease caused by an intracellular protozoan belonging to Leishmania species. Interleukin (IL)-22 plays an important role in inflammatory response, chemotaxis, regulation of cellular proliferation and tissue repair. Considering the role of IL-22 in control of leishmaniasis and the effect of its single nucleotide polymorphisms (SNPs) on respective function and production, this study aimed to investigate the probable association of IL-22 SNPs with VL.

LRP8 (rs5177) and CEP85L (rs11756438) are contributed to schizophrenia susceptibility in Iranian population.

Introduction Schizophrenia is recognized as one of the most important mental illnesses of the last century. Many genetic and environmental factors are involved in this condition. Recently, the genome-wide association study identified two significant genes LRP8 and CEP85L associated with psychiatric disorders.

Diverse phenotypic measurements of wellbeing: Heritability, temporal stability and the variance explained by polygenic scores.

Wellbeing, a key aspect of mental health, is moderately heritable with varying estimates reported from independent studies employing a variety of instruments. Recent genome-wide association studies (GWAS) have enabled the construction of polygenic scores (PGS) for wellbeing, providing the opportunity for direct comparisons of the variance explained by PGS for different instruments commonly employed in the field. Nine wellbeing measurements (multi-item and single-item), two personality domains (NEO-FFI neuroticism and extraversion), plus the depression domain of the DASS-42 were drawn from a larger self-report battery applied to the TWIN-E study-an Australian longitudinal twin cohort (N = 1660).

Electroencephalography profiles as a biomarker of wellbeing: A twin study.

Alterations to electroencephalography (EEG) power have been reported for psychiatric conditions such as depression and anxiety, but not for mental wellbeing in a healthy population. This study examined the resting EEG profiles associated with mental wellbeing, and how genetics and environment contribute to these associations using twin modelling. Mental wellbeing was assessed using the COMPAS-W Wellbeing Scale which measures both subjective and psychological wellbeing.

Phenotypic and genotypic characterization of families with complex intellectual disability identified pathogenic genetic variations in known and novel disease genes.

Intellectual disability (ID), which presents itself during childhood, belongs to a group of neurodevelopmental disorders (NDDs) that are clinically widely heterogeneous and highly heritable, often being caused by single gene defects. Indeed, NDDs can be attributed to mutations at over 1000 loci, and all type of mutations, ranging from single nucleotide variations (SNVs) to large, complex copy number variations (CNVs), have been reported in patients with ID and other related NDDs. In this study, we recruited seven different recessive NDD families with comorbidities to perform a detailed clinical characterization and a complete genomic analysis that consisted of a combination of high throughput SNP-based genotyping and whole-genome sequencing (WGS).

Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy.

The TWNK (C10orf2) gene encodes Twinkle, an essential helicase for mtDNA replication. Homozygous mutations in TWNK can lead to mitochondrial DNA depletion syndrome 7 (MTDPS7) that usually manifests as Infantile onset spinocerebellar ataxia (IOSCA). Here, we report a 15-year-old Iranian boy with three main symptoms; ataxia, sensorineural hearing loss and optic nerves atrophy which were accompanied by other symptoms including flexion contracture, dysarthric speech, nystagmus, dystonia and borderline intellectual disability.

Incomplete penetrance of gene for autosomal dominant form of cone-rod dystrophy.

: Cone-rod dystrophy (CRD) is an inherited retinal dystrophy that is transmitted via different modes of inheritance. Mutations in more than 30 genes have been identified to cause the disease. We aimed to investigate the genetic agents of two unrelated cone-rod dystrophy affected Iranian families with autosomal recessive inheritance patterns.

and rs35929607 polymorphisms and risk of Hypertension in Iranian Population.

ATP2B1 and STK39 have been introduced as essential hypertension candidate genes. The association of these genes' variations have not been studied in Iranian population yet. Here we aimed to investigate the association of ATP2B1 rs2681472 and STK39 rs35929607 polymorphisms with the risk of hypertension in an Iranian population.

Novel Mutations in Gene in Families with Gelatinous Drop-like Corneal Dystrophy (GDLD).

In the current study, we conducted a mutation screening of tumor-associated calcium signal transducer 2 () gene in six consanguineous Iranian families with gelatinous drop-like corneal dystrophy (GDLD), in order to find the causative mutations. Detailed eye examination was performed by ophthalmologist to confirm GDLD in patients. To detect the possible mutations, direct Sanger sequencing was performed for the only exon of gene, and its boundary regions in all patients.

A novel c.240_241insGG mutation in NDP gene in a family with Norrie disease.

Background: Norrie disease (ND) is a rare, X-linked recessive disorder with the main characteristic of early childhood blindness. The aim of the present study was to identify the genetic cause of the disease and the phenotypic characteristics of the patients in an Iranian family with four affected males with ND.

Methods: Norrie disease pseudoglioma (NDP) gene was sequenced and clinical examination was performed on patients.

A novel mutation in SMOC1 and variable phenotypic expression in two patients with Waardenburg anophthalmia syndrome.

Waardenburg anophthalmia syndrome (WAS) is a rare disorder that mostly affects the eyes and distal limbs. In the current study we reported two Iranian patients with WAS. The first case was a 26-year-old girl with unilateral anophthalmia, bilateral camptodactyly and clinodactyly in her hands, oligodactly in her left foot and syndactyly of the second to fifth toes in her right foot.

Support for "Disease-Only" Genotypes and Excess of Homozygosity at the CYTH4 Primate-Specific GTTT-Repeat in Schizophrenia.

Objective: The role of short tandem repeats (STRs) in the control of gene expression among species is being increasingly understood following the identification of several instances in which certain STRs occur identically, or expand differentially, in primates versus nonprimates. These STRs may regulate genes that participate in characteristics that are associated with the divergence of primates from sibling orders (e.g.

Association of renin-angiotensin-aldosterone system gene polymorphisms with left ventricular hypertrophy in patients with heart failure with preserved ejection fraction: A case-control study.

Background: Heart failure with preserved ejection fraction (HFpEF) has close ties with hypertension, though risk factors to the development of HFpEF in hypertensive patients are not fully understood. Left ventricular hypertrophy (LVH) signifies the susceptibility toward diastolic heart dysfunction, and genetic determinants of LVH as a result may serve as risk predictors for HFpEF in hypertension. We investigated the role of three renin-angiotensin-aldosterone system (RAAS) gene polymorphisms in the development of LVH in hypertensive patients with a diagnosis of HFpEF.

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism.

Association of β-Secretase Functional Polymorphism with Risk of Schizophrenia.

Aim: The NRG1-ERBB4 neurotransmitter signaling pathway plays a key role in the pathogenesis of schizophrenia (SZ). The intronic single-nucleotide polymorphism rs707284 in ERBB4 links to PI3K-AKT suppression in SZ. Another protein indirectly affecting NRG1-ERBB4 signaling is β-secretase, which is encoded by the BACE1 gene, and activates NRG1 by proteolytic cleavage.

Analysis of Copy Number Variations in Patients with Autism Using Cytogenetic and MLPA Techniques: Report of 16p13.1p13.3 and 10q26.3 Duplications.

Autism is a common neuropsychiatric disorder affecting 1 in 68 children. Copy number variations (CNVs) are known to be major contributors of autism spectrum disorder (ASD). There are different whole genome or targeted techniques to identify CNVs in the patients including karyotyping, multiplex ligation-dependent probe amplification (MLPA) and array CGH.

Omentin Val109Asp polymorphism and risk of coronary artery disease.

Background Omentin is an adipocytokine with antiinflammatory properties. It has been reported to be involved in atherosclerosis and coronary artery disease. We aimed to investigate the association of omentin Val109Asp polymorphism with coronary artery disease in an Iranian population.

RAB7L1 promoter polymorphism and risk of Parkinson's disease; a case-control study.

Introduction: Recent genome-wide association studies have explored some new loci in association with Parkinson's disease (PD). RAB7L1 is an important gene involved in one of the important neurological pathways, located in PARK16 locus. We performed a case-control study to examine the association between rs823144 SNP located in the promoter region of the RAB7L1 gene and PD risk in Iranian population.

Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome.

Autism is a common neurodevelopmental disorder estimated to affect 1 in 68 children. Many studies have shown the role of copy number variants (CNVs) as a major contributor in the etiology of autism with the overall detection rate of about 10-15 % and over 20 % when syndromic forms of autism exist. In this study, we used array CGH to identify CNVs in 15 Iranian patients with autism.