Clinical and molecular spectrum along with genotype-phenotype correlation of 25 patients diagnosed with 3 M syndrome: a study from Turkey.

Unlabelled: 3 M syndrome is a well-known autosomal recessive skeletal genetic disorder caused by biallelic pathogenic variants in the CUL7, OBSL1, and CCDC8 genes. Affected individuals exhibit profound pre- and postnatal growth retardation, distinctive facial features with normal intelligence. This study aims to provide insight into the comprehensive evaluation of clinical, laboratory, and radiological findings, expand the mutational spectrum of the disease, and establish a genotype-phenotype correlation in the present cases.

Association between the ARMS2 rs10490924 risk genotype and dry-age related macular degeneration patients with and without reticular pseudodrusen in a Turkish population: findings from a study conducted at a tertiary clinic.

Purpose: To evaluate the relationship between the presence of reticular pseudodrusen (RPD) and the risk allele of ARMS2 rs10490924 variation in dry-AMD patients by using multimodal imaging. Also, to compare patients with and without RPD and healthy volunteers according to the distribution of the risk allele.

Methods: In this cross-sectional study, dry-AMD patients with (Group A, n = 50) and without (Group B, n = 50) RPD and healthy volunteers (Group C, n = 50) were enrolled.

From Clinical Observation to Genetic Confirmation: Somatic Mosaic Mutations in RHOA on Ectodermal Dysplasia With Multi-System Involvement.

Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies (EDFAOB) is a rare neuroectodermal syndrome caused by somatic mosaic mutations in the RHOA gene. It presents with linear skin hypopigmentation, facial and limb asymmetry, dental and acral anomalies, and leukoencephalopathy, generally preserving intellectual and neurological functions. We report two cases of EDFAOB.

Utility of Optical Genome Mapping in Repeat Disorders.

Genomic repeat sequences are patterns of nucleic acids that exist in multiple copies throughout the genome. More than 60 Mendelian disorders are caused by the expansion or contraction of these repeats. Various specific methods for determining tandem repeat variations have been developed.

Diagnostic yield of exome sequencing-based copy number variation analysis in Mendelian disorders: a clinical application.

Next-generation sequencing (NGS) coupled with bioinformatic tools has revolutionized the detection of copy number variations (CNVs), which are implicated in the emergence of Mendelian disorders. In this study, we evaluated the diagnostic yield of exome sequencing-based CNV analysis in 449 patients with suspected Mendelian disorders. We aimed to assess the diagnostic yield of this recently utilized method and expand the clinical spectrum of intragenic CNVs.

"Predicting diabetic kidney disease in youth with type 1 diabetes: Insights from genetic risk assessment".

Objective: Diabetic kidney disease (DKD) is influenced by multiple factors, yet its precise progression mechanisms remain largely unclear. This study aimed to create a clinical risk-scoring system based on genetic polymorphisms in the AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, and ZMIZ1 genes.

Methods: The study included a DKD group diagnosed with diabetic kidney disease before age 18 and a WDC group matched by age, gender, and age at diabetes diagnosis.

Effectiveness of whole exome sequencing analyses in the molecular diagnosis of osteogenesis imperfecta.

Objectives: Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and to determine the relationship between genotype and phenotype in OI patients with whole exome sequencing (WES).

Methods: Multiplex-Ligation dependent Probe Amplification (MLPA) analysis of and and WES were performed on cases between the ages of 0 and 18 whose genetic etiology could not be determined before using a targeted next-generation sequencing panel, including 13 genes (, , , , , , , , , , , , ) responsible for OI.

The Utility of Genetic Testing in Infantile Epileptic Spasms Syndrome: A Step-Based Approach in the Next-Generation Sequencing Era.

Background: To evaluate the utility of genetic testing for etiology-specific diagnosis (ESD) in infantile epileptic spasms syndrome (IESS) with a step-based diagnostic approach in the next-generation sequencing (NGS) era.

Methods: The study cohort consisted of 314 patients with IESS, followed by the Pediatric Neurology Division of Ege University Hospital between 2005 and 2021. The ESD was evaluated using a step-based approach: step I (clinical phenomenology), step II (neuroimaging), step III (metabolic screening), and step IV (genetic testing).

Further defining the molecular spectrum and long-term follow-up of 17 patients with Dyggve-Melchior-Clausen and Smith-McCort dysplasia type 2.

Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and clinical findings. DMC and SMC type 1 are allelic disorders caused by homozygous or compound heterozygous variants in DYM, while biallelic causative variants in RAB33B lead to SMC type 2. The terminology "skeletal golgipathies" has been recently used to describe these conditions, highlighting the pivotal role of these two genes in the organization and intracellular trafficking of the Golgi apparatus.

Molecular Genetic Diagnosis with Targeted Next Generation Sequencing in a Cohort of Turkish Osteogenesis Imperfecta Patients and their Genotype-phenotype Correlation.

Objective: Osteogenesis imperfecta (OI) consists of a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. The aim was to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients using targeted next-generation sequencing (NGS).

Methods: A targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform in patients with a confirmed diagnosis of OI.

Identification of the molecular etiology in rare congenital hemolytic anemias using next-generation sequencing with exome-based copy number variant analysis.

Objectives: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA.

Methods: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study.

Molecular diagnosis in patients with monogenic diabetes mellitus, and detection of a novel candidate gene.

Aim: We aimed to investigate molecular genetic basis of monogenic diabetes (DM) and novel responsible candidate genes with targeted Next Generation Sequencing (NGS) and Whole Exome Sequencing (WES).

Methods: A hundred cases presenting with clinical findings and a family history of monogenic DM were included in the study. Molecular analysis was performed using an NGS panel including 14 genes.

A unique case of thrombophilia: the role of F9 gene duplication and increased factor IX activity in cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder characterized by the obstruction of venous channels in the brain. Genetic factors play a significant role in CVT development, and recent studies have identified gain-of-function mutations in coagulation factors, including factor IX (FIX). This case report focuses on a unique neonatal case of CVT, where an X-chromosome duplication involving the F9 gene resulted in increased FIX activity.

Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.

Aim: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up.

Methods: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months.

Pelvis Magnetic Resonance Imaging to Diagnose Familial Partial Lipodystrophy.

Context: The diagnosis of familial partial lipodystrophy (FPLD) is currently made based on clinical judgment.

Objective: There is a need for objective diagnostic tools that can diagnose FPLD accurately.

Methods: We have developed a new method that uses measurements from pelvic magnetic resonance imaging (MRI) at the pubis level.

LSM1 is the new candidate gene for neurodevelopmental disorder.

Neurodevelopmental disorders are a heterogeneous group of diseases. Clinical presentation often overlaps with neurodevelopmental disorders, and explaining the molecular origin often requires reverse phenotyping. Next-Generation Sequencing (NGS) allows fast and cost-effective high-throughput sequencing.

Mutation spectrum of the NF1 gene and genotype-phenotype correlations in Turkish patients: Seventeen novel pathogenic variants.

Objective: Neurofibromatosis type 1 is one of the most common autosomal dominant diseases caused by heterozygous mutation in the NF1 gene. Wide spectrum of NF1-related clinical manifestations and mutation distribution makes genetic counselling difficult.

Methods: The study enrolled 58 unrelated Turkish patients with clinically suspected NF1 referred to the Department of Medical Genetics.

The utility of reverse phenotyping: a case of lysinuric protein intolerance presented with childhood osteoporosis.

Objectives: Childhood osteoporosis is often a consequence of a chronic disease or its treatment. Lysinuric protein intolerance (LPI), a rare secondary cause of the osteoporosis, is an autosomal recessive disorder with clinical features ranging from minimal protein intolerance to severe multisystemic involvement. We report a case diagnosed to have LPI using a Next Generation Sequencing (NGS) panel and evaluate the utility of reverse phenotyping.