Estimating at-risk couple rates across 1000 exome sequencing data cohort for 176 genes and its importance relevance for health policies.

The development of high-throughput technologies has enabled Expanded Carrier screening (ECS) as a more comprehensive and extensive approach for high-risk populations. The available methods of ECS are population-targeted gene-panels according to ethnicity, however these panels should be planned according to a real-world data evaluation. In this study, we estimate the frequency of pathogenic variants for autosomal-recessive and X-linked conditions in Exome Sequencing-ES data for a 176 gene panel proposed from ACMG and ACOG in a Greek cohort.

Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a Case-Based Brief Review of the Literature.

Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic anemia. Life-threatening complications include progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), critical deep-tissue infections and asphyxiating thoracic dystrophy. In most patients, SDS results from biallelic pathogenic variants in the gene, different combinations of which contribute to heterogenous clinical presentations.

Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations.

, the gene encoding for the Nav1.1 channel, exhibits dominant interneuron-specific expression, whereby variants disrupting the channel's function affect the initiation and propagation of action potentials and neuronal excitability causing various types of epilepsy. Dravet syndrome (DS), the first described clinical presentation of SCN1A channelopathy, is characterized by severe myoclonic epilepsy in infancy (SMEI).

Myotonia congenita in a Greek cohort: Genotype spectrum and impact of the CLCN1:c.501C > G variant as a genetic modifier.

Introduction/aims: Myotonia congenita (MC) is the most common hereditary channelopathy in humans. Characterized by muscle stiffness, MC may be transmitted as either an autosomal dominant (Thomsen) or a recessive (Becker) disorder. MC is caused by variants in the voltage-gated chloride channel 1 (CLCN1) gene, important for the normal repolarization of the muscle action potential.

Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5].

De novo variants in RNF213 are associated with a clinical spectrum ranging from Leigh syndrome to early-onset stroke.

Purpose: RNF213, encoding a giant E3 ubiquitin ligase, has been recognized for its role as a key susceptibility gene for moyamoya disease. Case reports have also implicated specific variants in RNF213 with an early-onset form of moyamoya disease with full penetrance. We aimed to expand the phenotypic spectrum of monogenic RNF213-related disease and to evaluate genotype-phenotype correlations.

Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?

Chromosomal microarray analysis (CMA) is considered a first-tier test for patients with developmental disabilities and congenital anomalies and is also routinely applied in prenatal diagnosis. The current consensus size cut-off for reporting copy number variants (CNVs) in the prenatal setting ranges from 200 Kb to 400 Kb, with the intention of minimizing the impact of variants of uncertain significance (VUS). Very limited data are currently available on the application of higher resolution platforms prenatally.

Germline CNV Detection through Whole-Exome Sequencing (WES) Data Analysis Enhances Resolution of Rare Genetic Diseases.

Whole-Exome Sequencing (WES) has proven valuable in the characterization of underlying genetic defects in most rare diseases (RDs). Copy Number Variants (CNVs) were initially thought to escape detection. Recent technological advances enabled CNV calling from WES data with the use of accurate and highly sensitive bioinformatic tools.

Identification of a Novel Large Deletion through Copy Number Variant Analysis from Whole-Exome Sequencing Data of a Patient with Postaxial Polydactyly Type A7.

Introduction: Non-syndromic polydactyly has been associated with pathogenic variants in 11 genes until today, including gene. More precisely, loss-of-function of is associated with the autosomal recessive disorder postaxial polydactyly type A7 (PAPA7, MIM #617642).

Case Presentation: A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly, brachydactyly, and hypoplastic teeth.

Combined exome analysis and exome depth assessment achieve a high diagnostic yield in an epilepsy case series, revealing significant genomic heterogeneity and novel mechanisms.

Objectives: Genetics of epilepsy are highly heterogeneous and complex. Lesions detected involve genes encoding various types of channels, transcription factors, and other proteins implicated in numerous cellular processes, such as synaptogenesis. Consequently, a wide spectrum of clinical presentations and overlapping phenotypes hinders differential diagnosis and highlights the need for molecular investigations toward delineation of underlying mechanisms and final diagnosis.

A novel pathogenic ATP6V1B2 variant: Widening the genotypic spectrum of the epileptic neurodevelopmental phenotype.

ATP6V1B2 pathogenic variants are linked with variable phenotypes, such as dominant deafness-onychodystrophy syndrome (DDOD), autosomal dominant Zimmermann-Laband syndrome type 2 (ZLS2), and some cases of DOORS (deafness, onychodystrophy, osteodystrophy, intellectual disability [ID], and seizures). Epilepsy was first linked to ATP6V1B2, when the p.(Glu374Gln) missense variant was detected in a patient with ID and seizures, but without characteristic features of DDOD or ZLS2 syndromes.

Molecular and clinical profile of patients referred as Noonan or Noonan-like syndrome in Greece: a cohort of 86 patients.

Unlabelled: Noonan syndrome (NS) is an autosomal dominant disorder characterized by clinical and genetic heterogeneity. It belongs to a wider group of pathologies, known as Rasopathies, due to the implication of genes encoding components of the Ras/MAPK signalling pathway. Recording the genetic alterations across populations helps assessing specific features to specific genes which is essential for better disease's recognition, prognosis and monitoring.

Higher vitamin B6 status is associated with improved survival among patients with stage I-III colorectal cancer.

Background: Folate-mediated 1-carbon metabolism requires several nutrients, including vitamin B6. Circulating biomarker concentrations indicating high vitamin B6 status are associated with a reduced risk of colorectal cancer (CRC). However, little is known about the effect of B6 status in relation to clinical outcomes in CRC patients.

239-kb Microdeletion Spanning in a Child with Developmental Delay: Further Delineation of the Phenotype.

Pathogenic variants underly O'Donnell-Luria-Rodan syndrome, a recently described neurodevelopmental disorder characterized by global developmental delay, variable degrees of intellectual disability, and subtle facial dysmorphism. Less common findings include autism, seizures, gastrointestinal (GI) problems, and abnormal head circumference. Occurrence of mostly truncating variants as well as the similar phenotype observed in individuals with deletions spanning suggest haploinsufficiency of this gene as a common mechanism for the disorder, while a gain-of-function or dominant-negative effect cannot be ruled out for some missense variants.

Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders.

About 6000 to 7000 different rare disorders with suspected genetic etiologies have been described and almost 4500 causative gene(s) have been identified. The advent of next-generation sequencing (NGS) technologies has revolutionized genomic research and diagnostics, representing a major advance in the identification of pathogenic genetic variations. This study presents a 3-year experience from an academic genetics center, where 400 patients were referred for genetic analysis of disorders with unknown etiology.

A Spectrophotometric Study on Light Attenuation Properties of Dental Bleaching Gels: Potential Relevance to Irradiation Parameters.

Background: During in-office bleaching, appropriate light sources are applied in order to enhance the activity of the bleaching gels applied onto teeth. For this method to be effective, a high absorption of light within the gel is necessary. Variation in the light attenuation capability of the gel, the duration of application and light activation can contribute towards safety hazards associated with this procedure.

Circulating Folate and Folic Acid Concentrations: Associations With Colorectal Cancer Recurrence and Survival.

Background: Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown.

Development of a multidisciplinary clinic of neurofibromatosis type 1 and other neurocutaneous disorders in Greece. A 3-year experience.

Given the complexity of neurocutaneous syndromes, a multidisciplinary approach has been advocated in order to provide optimum care. Retrospective analysis of a cohort of 157 patients during a 3-year period, seen at a newly developed neurocutaneous clinic in a pediatric tertiary care hospital in Athens (Greece); and systematic chart review of the patients diagnosed with neurofibromatosis type 1 during this time period. The most frequent neurocutaneous syndromes were neurofibromatosis type 1 (NF1) in 89 patients and tuberous sclerosis complex in 17.

Impact of Relative Humidity on Wood Sample: A Climate Chamber Experimental Simulation Monitored by Digital Holographic Speckle Pattern Interferometry.

Relative humidity (RH) changes are a natural environmental effect that forces organic materials to a constant cycle of achieving equilibrium. The present work is part of an ongoing research based on the hypothesis that the inevitable deleterious effects of the RH natural cycle may be prevented or minimized if a deformation threshold is assigned to each monitored endangered object prior to exposure to structural damage. In this paper the characterization of the behavior of a softwood sample (1.

A Female Patient with Xq28 Microduplication Presenting with Myotubular Myopathy, Confirmed with a Custom-Designed X-array.

X-linked myotubular myopathy (XLMTM) is a rare inherited neuromuscular disorder associated with mutations in the gene on the Xq28 region. We report a severely affected girl with XLMTM, caused by maternally inherited 661 kb Xq28 microduplication identified by chromosomal microarray analysis and confirmed also on DNA from muscle biopsy with a custom-designed X-chromosome-specific microarray. X-inactivation analysis revealed a skewed inactivation pattern on the proband's muscle biopsy.

Multiple Light Coupling and Routing via a Microspherical Resonator Integrated in a T-Shaped Optical Fiber Configuration System.

We demonstrate a three-port, light guiding and routing T-shaped configuration based on the combination of whispering gallery modes (WGMs) and micro-structured optical fibers (MOFs). This system includes a single mode optical fiber taper (SOFT), a slightly tapered MOF and a BaTiO₃ microsphere for efficient light coupling and routing between these two optical fibers. The BaTiO₃ glass microsphere is semi-immersed into one of the hollow capillaries of the MOF taper, while the single mode optical fiber taper is placed perpendicularly to the latter and in contact with the equatorial region of the microsphere.

Phenotypic expression of a spectrum of Neurofibromatosis Type 1 (NF1) mutations identified through NGS and MLPA.

Neurofibromatosis Type 1 (NF1) is caused by mutations of the NF1 gene. The aim of this study was to identify the genetic causes underlying the disease, attempt possible phenotype/genotype correlations and add to the NF1 mutation spectrum. A screening protocol based on genomic DNA was established in 168 patients, encompassing sequencing of all coding exons and adjoining introns using a custom targeted next generation sequencing protocol and subsequent confirmation of findings with Sanger sequencing.