Expanding TBCE-related phenotype-novel variant causing rigid spine, eosinophilia, neutropenia, and nocturnal hypoxemia.

We report three patients with the novel variant c.100 + 1G > A of the TBCE gene and describe the presented clinical phenotype in detail. We also systematically reviewed the literature for clinical similarities and dissimilarities among all known patients with pathogenic TBCE variants.

Optimised, Broad NGS Panel for Inherited Eye Diseases to Diagnose 1000 Patients in Poland.

Advances in gene therapy and genome editing give hope that new treatments will soon be available for inherited eye diseases that together affect a significant proportion of the adult population. New solutions are needed to make genetic diagnosis fast and affordable. This is the first study of such a large group of patients with inherited retinal dystrophies (IRD) and inherited optic neuropathies (ION) in the Polish population.

The landscape of the COVID-19 pandemic in Poland emerging from epidemiological and genomic data.

The COVID-19 pandemic has profoundly affected all aspects of our lives. Through real-time monitoring and rapid vaccine implementation, we succeeded in suppressing the spread of the disease and mitigating its consequences. Finally, conclusions can be summarized and drawn.

Coexistence of Retinitis Pigmentosa and Ataxia in Patients with PHARC, PCARP, and Oliver-McFarlane Syndromes.

Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and retinal pigment epithelial atrophy, leading to severe visual impairment or blindness. RP can be classified as nonsyndromic or syndromic with complex clinical phenotypes. Three unrelated Polish probands affected with retinitis pigmentosa coexisting with cerebellar ataxia were recruited for this study.

Are Young People with Turner Syndrome Who Have Undergone Treatment with Growth and Sex Hormones at Higher Risk of Metabolic Syndrome and Its Complications?

Introduction: Metabolic syndrome (MetS), characterized by visceral obesity, glucose abnormalities, hypertension and dyslipidemia, poses a significant risk of diabetes and cardiovascular disease. Turner syndrome (TS), resulting from X chromosome abnormalities, carries health complications. Despite growing evidence of an increased risk of MetS in women with TS, its prevalence and risk factors remain under investigation.

Validation of targeted next-generation sequencing panels in a cohort of Polish patients with epilepsy: assessing variable performance across clinical endophenotypes and uncovering novel genetic variants.

Introduction: Targeted Next-Generation Sequencing Panels (TNGSP) have become a standard in global clinical practice. Instead of questioning the necessity of next-generation sequencing in epilepsy patients, contemporary large-scale research focuses on factors such as the size of TNGSP, the comparative advantages of exome or genome-wide sequencing over TNGSP, and the impact of clinical, electrophysiological, and demographic variables on genetic test performance. This study aims to elucidate the demographic and clinical factors influencing the performance of TNGSP in 138 Polish patients with epilepsy, recognizing the pivotal role of genetic testing in guiding patient management and therapy.

Molecular landscape of congenital vertebral malformations: recent discoveries and future directions.

Vertebral malformations (VMs) pose a significant global health problem, causing chronic pain and disability. Vertebral defects occur as isolated conditions or within the spectrum of various congenital disorders, such as Klippel-Feil syndrome, congenital scoliosis, spondylocostal dysostosis, sacral agenesis, and neural tube defects. Although both genetic abnormalities and environmental factors can contribute to abnormal vertebral development, our knowledge on molecular mechanisms of numerous VMs is still limited.

Development of a tool for predicting HNF1B mutations in children and young adults with congenital anomalies of the kidneys and urinary tract.

Background: We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT).

Methods: The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%).

Chromatinopathies: insight in clinical aspects and underlying epigenetic changes.

Chromatinopathies (CPs), a group of rare inborn defects characterized by chromatin state imbalance, have evolved from initially resembling Cornelia de Lange syndrome to encompass a wide array of genetic diseases with diverse clinical presentations. The CPs classification now includes human developmental disorders caused by germline mutations in epigenes, genes that regulate the epigenome. Recent advances in next-generation sequencing have enabled the association of 154 epigenes with CPs, revealing distinctive DNA methylation patterns known as episignatures.

The Interplay between Muscular Grip Strength and Bone Mineral Density with Consideration of Metabolic and Endocrine Parameters in Individuals with Turner Syndrome.

Introduction: Patients with Turner syndrome (TS) often face skeletal and muscular challenges, including reduced bone mineral density (BMD) and muscle weakness. This comprehensive study sheds light on the complex interplay between muscle strength, BMD, and metabolic and endocrine parameters in TS and healthy subjects.

Methods: A cross-sectional study involving 42 TS patients and 70 healthy women was conducted.

A genotype-phenotype correlation in split-hand/foot malformation type 1: further refinement of the phenotypic subregions within the 7q21.3 locus.

Split-hand/foot malformation type 1 (SHFM1) refers to the group of rare congenital limb disorders defined by the absence or hypoplasia of the central rays of the autopods with or without accompanying anomalies, such as hearing loss, craniofacial malformation, and ectodermal dysplasia. Consequently, the condition is characterized by clinical variability that hinders diagnostic and counseling procedures. SHFM1 is caused by pathogenic variants affecting the genes and/or their tissue-specific enhancers at the 7q21.

The clinical phenotype with gastrostomy and abdominal wall infection in a pediatric patient with Takenouchi-Kosaki syndrome due to a heterozygous c.191A > G (p.Tyr64Cys) variant in : a case report.

The (cell division cycle homolog 42) gene product, Cdc42 belongs to the Rho GTPase family which plays a pivotal role in the regulation of multiple cellular functions, including cell cycle progression, motility, migration, proliferation, transcription activation, and reactive oxygen species production. The Cdc42 molecule controls various tissue-specific functional pathways underpinning organogenesis as well as developmental integration of the hematopoietic and immune systems. Heterozygous c.

-Related Cone-Rod Dystrophy: Clinical Characteristics, Imaging Findings, and Genetic Test Results-A Case Report.

Cone-rod dystrophies (CRDs) are a heterogeneous group of inherited retinal diseases (IRDs) characterized by cone photoreceptor loss, that is followed by subsequent rod photoreceptor impairment. A 49-year-old man complaining of diminution of vision in both eyes (OU) was referred to our outpatient clinic. He reported visual loss for 5 years, but it was most progressive during the last few months.

Molecular Re-Diagnosis with Whole-Exome Sequencing Increases the Diagnostic Yield in Patients with Non-Syndromic Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of disorders with progressive loss of photoreceptor and pigment epithelial function. Nineteen unrelated Polish probands clinically diagnosed with nonsyndromic RP were recruited to this study. We used whole-exome sequencing (WES) to identify potential pathogenic gene variants in molecularly undiagnosed RP patients, as a molecular re-diagnosis after having performed targeted NGS in the past.

Broadening the phenotypic spectrum of the presumably epilepsy-related SV2A gene variants.

Missense variants in the synaptic vesicle glycoprotein SV2A gene have been previously found in a few individuals with epilepsy. Adverse reaction to levetiracetam in individuals with various variants of this gene has recently been described. Here, we report on a family with several members affected by epilepsy.

A pure de novo 16p13.3 duplication and amplification in a patient with femoral hypoplasia, psychomotor retardation, heart defect, and facial dysmorphism-a case report and literature review of the partial 16p13.3 trisomy syndrome.

Partial 16p trisomy syndrome is a rare disorder typically characterized by psychomotor retardation, prenatal and postnatal growth deficiency, cleft palate, and facial dysmorphism, with some patients also presenting with heart defects and urogenital anomalies. Pure 16p13.3 duplications usually occur de novo, while those duplications that associate with partial monosomy result rather from parental chromosomal translocations.

Rare multiple congenital anomalies-hypotonia-seizures syndrome type 1 (MCAHS1) - the clinical and molecular summary.

Multiple congenital anomalies-hypotonia-seizures syndrome type 1 (MCAHS1) is a rare autosomal recessive genetic disease belonging to glycosylphosphatidylinositols biosynthesis defects (GPIBD), a group of recessive disorders characterized by intellectual disability, hypotonia, and seizures. Glycosylphosphatidylinositols (GPIs) are glycolipids that anchor and remodel cell proteins. These processes are highly conserved and fundamental in the metabolism of all eukaryotes, including humans.

Molecular background of Leber congenital amaurosis in a Polish cohort of patients-novel variants discovered by NGS.

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophies and the most frequent cause of congenital blindness in children. To date, 25 genes have been implicated in the pathogenesis of this rare disorder. Performing an accurate molecular diagnosis is crucial as gene therapy is becoming available.

SHFLD3 phenotypes caused by 17p13.3 triplication/ duplication encompassing Fingerin (BHLHA9) invariably.

Background: Split-hand/ foot malformation with long bone deficiency 3 (SHFLD3) is an extremely rare condition associated with duplications located on 17p13.3, which invariably encompasses the BHLHA9 gene. The disease inherits with variable expressivity and significant incomplete penetrance as high as 50%.

WDR35 variants in a cranioectodermal dysplasia patient with early onset end-stage renal disease and retinal dystrophy.

Cranioectodermal dysplasia (CED) is rare heterogeneous condition. It belongs to a group of disorders defined as ciliopathies and is associated with defective cilia function and structure. To date six genes have been associated with CED.

The pZRS non-coding regulatory mutation resulting in triphalangeal thumb-polysyndactyly syndrome changes the pattern of local interactions.

Herein, we report on a large Polish family presenting with a classical triphalangeal thumb-polysyndactyly syndrome (TPT-PS). This rare congenital limb anomaly is generally caused by microduplications encompassing the Sonic Hedgehog (SHH) limb enhancer, termed the zone of polarizing activity (ZPA) regulatory sequence (ZRS). Recently, a pathogenic variant in the pre-ZRS (pZRS), a conserved sequence located near the ZRS, has been described in a TPT-PS Dutch family.

Clinical and immunological assessment of APDS2 with features of the SHORT syndrome related to a novel mutation in with reduced penetrance.

Monoallelic loss-of-function (LOF) mutations in the phosphatidylinositol 3-kinase () gene affecting the inter-Src homology 2 domain of the p85α regulatory subunit of phosphoinositide--3-kinase δ (PI3Kδ) cause the activated PI3K δ syndrome (APDS2). APDS2 is defined as a primary antibody deficiency, developmental abnormalities within the B and T lymph cell compartments, and immune dysregulation. The genetic defect of APDS2 is shared with that of the SHORT syndrome, characterized by short stature, joint hyperextensibility, ocular depression, Rieger anomaly, and delayed tooth eruption.

Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects.

Craniosynostosis (CS) represents a highly heterogeneous genetic condition whose genetic background has not been yet revealed. The abnormality occurs either in isolated form or syndromic, as an element of hundreds of different inborn syndromes. Consequently, CS may often represent a challenging diagnostic issue.

An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population.

Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.