Shared molecular profiles of post-laser vision correction ectasia and keratoconus with key differences in , , , and .

Introduction: Post-laser vision correction (post-LVC) ectasia is a serious complication that is observed in 0.033%-0.66% of corneal refractive surgeries.

Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin gene.

Senataxin, an RNA/DNA helicase, is a key protein providing genome stability and one of the best characterized R-loop-binding factors playing an important role in transcription and DNA repair processes. Pathogenic SETX gene variants cause autosomal recessive spinocerebellar ataxia with axonal neuropathy (AOA2, MIM #606002) and autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4, MIM #602433), rare neurodegenerative disorders characterized by juvenile onset of progressive cerebellar ataxia, axonal sensorimotor peripheral neuropathy, combined upper and lower motor neuron symptoms, and increased serum alpha-fetoprotein (AFP; specific for AOA2). We report two cases of adult patients presenting with cerebellar syndrome, scanned speech, and exercise intolerance which started in the second/third decade of life and were followed by muscle weakness and impaired gait coordination.

Prevalence of intronic repeat expansions in the RFC1 gene in Polish patients with cerebellar syndrome.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited neurodegenerative ataxic disorder, which has been associated with intronic biallelic repeat expansions in the RFC1 gene. Our objective was to assess retrospectively the prevalence of CANVAS in Polish population. We screened 2523 Polish patients in whom other repeat expansions were excluded.

Genetic architecture of dilated cardiomyopathy in Poland: variant distribution, clinical characteristics and prognosis.

Introduction:  Genetic variants are the leading cause of dilated cardiomyopathy (DCM). Data on genetic testing in DCM from Central European populations are scarce.

Objectives:  We sought to determine the genetic architecture of DCM in Poland and assess its influence on clinical characteristics and prognosis.

Mixed Segmental Uniparental Disomy of Chromosome 15q11-q1 Coexists with Homozygous Variant in Gene in Child with Prader-Willi and Lodder-Merla Syndrome.

Background: Uniparental disomy (UPD) refers to the condition in which both chromosomes (or part of chromosome) of a pair are inherited from the same parent. There are two types of UPD: uniparental isodisomy (both chromosomes inherited from one parent are identical copies) and uniparental heterodisomy (two different chromosomes are inherited from one parent). UPD presents two primary developmental risks: recessive trait inheritance or an imprinting disorder.

The Attenuated Phenotype of CNTNAP1-Related Neuropathy Mimics Spastic-Dystonic Cerebral Palsy.

CNTNAP1 encodes a contactin-associated protein 1, which is essential for formation and organization of myelinated nerve fibers. Biallelic pathogenic variants in CNTNAP1 cause a severe congenital hypomyelinating neuropathy, characterized by hypotonia, arthrogryposis, respiratory failure, and early lethality. We describe two brothers, seven and 13 years old, with spastic tetraparesis and limb dystonia, in whom we identified compound heterozygous variants in CNTNAP1.

Maternal Uniparental Isodisomy of Chromosome 6: A Novel Case of Teratoma and Autism Spectrum Disorder with a Diagnostic and Management Framework.

Background: Uniparental disomy (UPD) is the inheritance of both copies of a chromosome from a single parent, leading to distinct genetic conditions. Maternal UPD of chromosome 6 (UPD(6)mat) is extremely rare, with few molecularly confirmed cases reported.

Methods: We report a prematurely born female with isodisomic UPD(6)mat, presenting with intrauterine growth restriction (IUGR), developmental delay, autism spectrum disorder, dysmorphic features, and a sacrococcygeal teratoma.

Coupling deep phenotypic quantification with next-generation phenotyping for 192 individuals with germline histonopathies.

Mendelian histonopathies are rare neurodevelopmental disorders (NDDs) caused by germline variants in histone-encoding genes. Here, we perform a more expansive pan-histonopathy interrogation than previously possible. We analyze data from 192 individuals affected by histonopathies.

gene duplication as the possible cause of massive hyperammonaemia with a fatal prognosis.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It may occur due to various changes to the gene located on the X chromosome. Many sequence variants in the gene result in different severity and require different types of molecular testing.

Inherited and de novo variants in young females potentially associated with pelvic organ prolapse.

Background: Pelvic organ prolapse is a common condition usually affecting postmenopausal women, but it is also seen in about 10% of women aged 20 to 39 years. In young females, genetic factors seem to be of particular interest.

Objective: This study aimed to identify inherited and de novo variants relevant to pelvic organ prolapse in young females without a family history.

Syndrome: Clinical Features, Imaging Findings and Cardiac Events.

syndrome (PS) is a rare genocopy of hypertrophic cardiomyopathy (HCM). Our goal was to expand knowledge about PS by analyzing patient clinical, imaging, and follow-up data. : The study included carriers of likely pathogenic or pathogenic variants identified in the years 2011-2022.

Decreased Level of TMEM100 in Neonates With Lethal Lung Developmental Disorders due to Abnormalities in SHH-FOXF1 and TBX4-FGF10 Signaling Pathways.

Lethal lung developmental disorders (LLDDs), histologically classified as alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), congenital alveolar dysplasia (CAD), acinar dysplasia (AcDys), and primary pulmonary hypoplasia (PH), are rare diseases associated with high neonatal mortality due to refractory respiratory failure. Although ACDMPV mostly results from single nucleotide variants (SNVs) or copy-number variants (CNVs) involving FOXF1, AcDys, CAD, and PH are often associated with abnormalities within TBX4 or FGF10. These genes interact in the SHH-FOXF1 and TBX4-FGF10 signaling network and are known regulators of lung development.

Case Report: Cholestatic liver disease in the course of erythropoietic protoporphyria associated with renal hypodysplasia and atrial septal defect.

Erythropoietic protoporphyria (EPP) is an autosomal recessive disorder of the heme biosynthesis pathway caused by pathogenic variants in gene resulting in a decreased activity of ferrochelatase. Liver involvement is observed in 5%-20% of patients harbouring loss-of-function variants and its manifestations are heterogeneous, ranging from mildly elevated liver transaminases, cholelithiasis to severe acute cholestatic hepatitis/liver failure. This paper presents the case of a Polish infant with EPP associated with two novel missense variants accompanied by other congenital anomalies, namely atrial septal defect and renal hypodysplasia.

Molecular Review of Suspected Alport Syndrome Patients-A Single-Centre Experience.

Alport syndrome (AS) is a clinically and genetically heterogeneous glomerulopathy resulting from pathogenic variants in and . Genetic diagnosis is increasingly being conducted using next-generation sequencing (NGS). Within eight years, we examined a group of 247 Polish individuals and found in total 138 unrelated probands suspected with AS based on clinical course, laboratory findings, and/or family history, as well as the total of 109 family members.

De novo variants in RYBP are associated with a severe neurodevelopmental disorder and congenital anomalies.

Purpose: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.

Complementarity of biomarker screening and genetic analyses based on the case of an attenuated multiple sulfatase deficiency.

Multiple sulfatase deficiency (MSD) is an ultra-rare lysosomal disease caused by defective activation of cellular sulfatases comprising clinical features of mucopolysaccharidoses, sphingolipidoses, and other sulfatase deficiencies. We present a case of an infant with feeding difficulties related to autism spectrum disorder (ASD) who was diagnosed at 10 months of age with MSD by next-generation sequencing (NGS). Biochemical results obtained in dried blood spot (DBS) samples were inconsistent and not suggesting MSD in the light of identified pathogenic SUMF1 variants.

Non-infectious mixed cryoglobulinemia as a new clinical presentation of mutation in the gene encoding coatomer subunit alpha: a case report of two adult sisters.

Cryoglobulinemia is a rare disease characterized by the presence of cryoglobulins in the blood serum. It is usually caused by autoimmune, lymphoproliferative, or infectious factors. The pathogenesis of cryoglobulinemia is not well understood, therefore, genetic testing is very important.

DNA methylation dysregulation patterns in the 1p36 region instability.

In the monosomy 1p36 deletion syndrome, the role of DNA methylation in the genomic stability of the 1p36 region remains elusive. We hypothesize that changes in the methylation pattern at the 1p36 breakpoint hotspot region influenced the chromosomal breakage leading to terminal deletions. From the monosomy 1p36 material collection, four cases with 4.

Mutation in the mitochondrial chaperone TRAP1 leads to autism with more severe symptoms in males.

There is increasing evidence of mitochondrial dysfunction in autism spectrum disorders (ASD), but the causal relationships are unclear. In an ASD patient whose identical twin was unaffected, we identified a postzygotic mosaic mutation p.Q639* in the TRAP1 gene, which encodes a mitochondrial chaperone of the HSP90 family.

The epilepsy phenotype of KCNK4-related neurodevelopmental disease.

Introduction: Potassium ion channels play a crucial role in maintaining cellular electrical stability and are implicated in various epilepsies. Heterozygous pathogenic variants in KCNK4 cause a recognizable neurodevelopmental syndrome with facial dysmorphism, hypertrichosis, epilepsy, intellectual disability (ID), and gingival overgrowth (FHEIG). To date, no more than nine patients with FHEIG have been described worldwide and still little is known about epileptic phenotype in KCNK4-related disease.