Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia.

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum.

ACER3-related leukoencephalopathy: expanding the clinical and imaging findings spectrum due to novel variants.

Background: Leukodystrophies are the main subgroup of inherited CNS white matter disorders which cause significant mortality and morbidity in early years of life. Diagnosis is mostly based on clinical context and neuroimaging findings; however, genetic tools, particularly whole-exome sequencing (WES), have led to comprehending the causative gene and molecular events contributing to these disorders. Mutation in Alkaline Ceramidase 3 (ACER3) gene which encodes alkaline ceramidase enzyme that plays a crucial role in cellular growth and viability has been stated as an uncommon reason for inherited leukoencephalopathies.

Comprehensive Mutation Analysis and Report of 12 Novel Mutations in a Cohort of Patients with Spinal Muscular Atrophy in Iran.

Spinal muscular atrophies (SMAs) are a heterogeneous group of neuromuscular diseases characterized by loss of motor neurons, muscle weakness, hypotonia and muscle atrophy, with different modes of inheritance; however, the survival motor neuron 1 (SMN1) gene is predominantly involved. The aims of the current study were to clarify the genetic basis of SMA and determine the mutation spectrum of SMN1 and other associated genes, in order to provide molecular information for more accurate diagnosis and future prospects for treatment. We performed a comprehensive analysis of 5q SMA in 1765 individuals including 528 patients from 432 unrelated families with at least one child with suspected clinical presentation of SMA.

Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population.

Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, characterized by intellectual deficit and neuropsychiatric complications in untreated patients with estimated frequency of about one in 10,000 to 15,000 live births. PAH deficiency can be detected by neonatal screening in nearly all cases with hyperphenylalaninemia on a heel prick blood spot. Molecular testing of the PAH gene can then be performed in affected family members.

Lack of association between FTO gene variations and metabolic healthy obese (MHO) phenotype: Tehran Cardio-metabolic Genetic Study (TCGS).

Background: Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes.

Anti‑inflammatory effect of Migri‑Heal® in an in vitro inflammatory model of primary mixed glial cells.

Migri‑Heal®, is a novel herbal remedy that was introduced for the treatment of migraine headaches. Previous studies revealed that this drug may reduce nitric oxide (NO) in an in vitro inflammatory model. The aim of the present study was to investigate the anti‑inflammatory effect of Migri‑Heal® on primary mix glial cells stimulated with LPS.

Increased Risk of CHD in the Presence of rs7865618 (A allele): Tehran Lipid and Glucose Study.

Background: Recent genome-wide association studies (GWAS) in European populations have indicated that the rs12526453 polymorphism located in phosphatase and actin regulator 1 gene (PHACTR1), mapping to chromosome 6p24 and rs7865618 polymorphism in the cyclin-dependent kinase inhibitor B antisense RNA 1 gene (CDKN2B-AS1) on 9p21.3 are associated with coronary heart disease (CHD). This study was carried out to investigate the association of these polymorphisms and CHD in an Iranian population.

Rationale and Design of a Genetic Study on Cardiometabolic Risk Factors: Protocol for the Tehran Cardiometabolic Genetic Study (TCGS).

Background: Cardiometabolic risk factors comprise cardiovascular diseases and/or diabetes, and need to be evaluated in different fields.

Objective: The primary aim of the Tehran Cardiometabolic Genetic Study (TCGS) is to create a comprehensive genome-wide database of at least 16,000 Tehranians, who are participants of the ongoing Tehran Lipid and Glucose Study (TLGS) cohort.

Methods: TCGS was designed in collaboration with the Research Institute for Endocrine Sciences and the genetic company deCODE.

A Large Cohort Study of Genotype and Phenotype Correlations of Beta- Thalassemia in Iranian Population.

Background: Thalassemia syndromes are the most prevalent single gene disorders in Iran. This study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or Xmn1 SNP on disease phenotype in a large cohort of Iranian patients.

Subjects And Methods: In total, 433 patients were clinically classified into β-thalassemia major (TM) or intermedia (TI).

The Relation between Metabolic Syndrome Risk Factors and Genetic Variations of Apolipoprotein V in Relation with Serum Triglyceride and HDL-C Level.

Introduction: Metabolic syndrome (MetS) is a multi-factorial disorder with five important components. A high triglyceride level combined with low HDL cholesterol has been reported to be associated with Apolipoprotein A5 (APOA5) gene variations. In this study, we aimed to determine the association of single nucleotide polymorphisms including: rs662799, rs3135506 and rs2075291 in the apolipoprotein A-V (APOA5) gene in relation to MetS component like triglyceride and HDL-C level in Tehran Lipid and Glucose Study (TLGS).

Allelic heterogeneity among Iranian DFNB7/11 families: report of a new Iranian deaf family with TMC1 mutation identified by next-generation sequencing.

Conclusion: Co-segregation of c.2030T>C mutation with hearing loss in an Iranian family and absence of this mutation in 100 Iranian controls confirms the pathogenicity of this mutation. Allelic heterogeneity among Iranian DFNB7/11 families has been shown by the identification of six different mutations in eight families.

Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes.

Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114 Icelandic cases and 267,140 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.

Reporting the presence of three different diseases causing GJB2 mutations in a consanguineous deaf family.

Objective: This paper reports a consanguineous deaf family with three different mutations in the GJB2 gene.

Design: Four members of an Iranian deaf family were recruited in this study. The GJB2 coding region and exon-intron boundaries were investigated using direct sequencing.

The projection of burden of disease in Islamic Republic of Iran to 2025.

Objective: Iran as a developing country is in the transition phase, which might have a big impact on the Burden of Disease and Injury (BOD). This study aims to estimate Burden of Disease and Injury (BOD) in Iran up to 2025 due to four broad cause groups using Disability-Adjusted Life Year (DALY).

Methods: The impacts of demographic and epidemiological changes on BOD (DemBOD and EpiBOD) were assessed separately.

Heritability of the metabolic syndrome and its components in the Tehran Lipid and Glucose Study (TLGS).

Growing evidence suggests that metabolic syndrome (MetS) has both genetic and environmental bases. We estimated the heritability of the MetS and its components in the families from the Tehran Lipid and Glucose Study (TLGS). We investigated 904 nuclear families in TLGS with two biological parents and at least one offspring (1565 parents and 2448 children), aged 3-90 years, for whom MetS information was available and had at least two members of family with MetS.

A 10-year study of esophageal cancer in Guilan province, Iran: the Guilan Cancer Registry Study (GCRS).

Background: Northern Iran counts as one of the highest prevalence regions for esophageal cancer (EC) worldwide. This study was designed to assess the epidemiologic aspects of EC in north central and northwest Iran over a 10 year period.

Materials And Methods: The Guilan cancer registry study (GCRS) is a population- based cancer registry study featuring retrospective (1996-2003) and prospective (2004-2005) phases.

Development of a quantitative real-time PCR assay for detection of unknown alpha-globin gene deletions.

Background: Alpha-Thalassemia is the most common inherited disorder of hemoglobin (Hb) synthesis in the world. Unlike beta-thalassemia, in which non-deletional mutations predominate, most of recognized alpha-thalassemia mutations include deletion of one or both alpha-globin genes. The importance of alpha-thalassemia detection is mainly due to its shared blood parameters with beta-thalassemia and its impact on discrimination between unknown alpha-thalassemia and normal HbA2 beta-thalassemia during thalassemia prevention program.