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.

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.

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.

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.

The clinical phenotype of Koolen-de Vries syndrome in Turkish patients and literature review.

Koolen-de Vries syndrome (KdVS) is a rare multisystemic disorder caused by a microdeletion on chromosome 17q21.31 including KANSL1 gene or intragenic pathogenic variants in KANSL1 gene. Here, we describe the clinical and genetic spectrum of eight Turkish children with KdVS due to a de novo 17q21.

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.