Adipose-Derived Mesenchymal Stem Cells from Arthritis Patients: Differential Modulation of CD4⁺ T Cell Activation and Cytokine Production.

BACKGROUND Adipose-derived stem cells (ASCs) from intra-articular adipose tissue of osteoarthritis (OA) and rheumatoid arthritis (RA) patients similarly regulate the proliferation of activated CD4⁺ T lymphocytes and exhibit comparable differentiation potential. This study aimed to assess the impact of ASCs from RA patients on CD4⁺ T cell activation and differentiation into Th17 and T regulatory (Treg) cells. MATERIAL AND METHODS Intra-articular adipose tissue samples were obtained from patients with RA and OA, who underwent knee replacement surgery.

Good vision without peripheries: behavioral and fMRI evidence.

In healthy vision, bright slow-motion stimuli are processed primarily by the regions of the visual system that receive input from the central part of the scene, whereas processing of dark fast-motion stimuli is more dependent on peripheral visual input. We tested 31 retinitis pigmentosa (RP) patients with long-term loss of peripheral photoreceptors and healthy controls with temporarily limited peripheral vision. We measured motion-based acuity using random-dot kinematograms, establishing individual thresholds for differentiating a circle from an ellipse.

Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.

Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients.

Leber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial DNA. Recently, an autosomal recessive form of LHON (LHONAR1, arLHON) has been discovered, caused by biallelic variants in the gene.

Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss.

Background: Low-frequency non-syndromic hearing loss (LFNSHL) is a rare form of hearing loss (HL). It is defined as HL at low frequencies (≤2,000 Hz) resulting in a characteristic ascending audiogram. LFNSHL is usually diagnosed postlingually and is progressive, leading to HL affecting other frequencies as well.

MMP-9 plasma level as biomarker of cochlear implantation outcome in cohort study of deaf children.

Purpose: If before cochlear implantation it was possible to assay biomarkers of neuroplasticity, we might be able to identify those children with congenital deafness who, later on, were at risk of poor speech and language rehabilitation outcomes.

Methods: A group of 40 children aged up to 2 years with DFNB1-related congenital deafness was observed in this prospective cohort study over three follow-up intervals (0, 8, and 18 months) after cochlear implant (CI) activation. Children were assessed for auditory development using the LittlEARS Questionnaire (LEAQ) score, and at the same time, measurements were made of matrix metalloproteinase-9 (MMP-9) plasma levels.

Longitudinal Changes in BDNF and MMP-9 Protein Plasma Levels in Children after Cochlear Implantation.

Congenitally deaf children who undergo cochlear implantation before 1 year of age develop their auditory skills faster than children who are implanted later. In this longitudinal study, a cohort of 59 implanted children were divided into two subgroups according to their ages at implantation-below or above 1 year old-and the plasma levels of matrix metalloproteinase-9 (MMP-9), brain-derived neurotrophic factor (BDNF), and pro-BDNF were measured at 0, 8, and 18 months after cochlear implant activation, while auditory development was simultaneously evaluated using the LittlEARs Questionnaire (LEAQ). A control group consisted of 49 age-matched healthy children.

The Genetic Background of Hearing Loss in Patients with EVA and Cochlear Malformation.

The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic variants are considered the major cause of inner ear malformation but the genetics still needs clarification.

Minigene-Based Splice Assays Reveal the Effect of Non-Canonical Splice Site Variants in .

Non-canonical splice site variants are increasingly recognized as a relevant cause of the -associated diseases, non-syndromic autosomal recessive retinitis pigmentosa and Usher syndrome type 2. Many non-canonical splice site variants have been reported in public databases, but an effect on pre-mRNA splicing has only been functionally verified for a subset of these variants. In this study, we aimed to extend the knowledge regarding splicing events by assessing a selected set of non-canonical splice site variants and to study their potential pathogenicity.

Hearing Loss as the Main Clinical Presentation in -Associated Autoinflammatory Disease.

The gene mutations are the cause of autosomal dominant autoinflammatory disorders (NLRP3-AID). Recently, hearing loss (HL) has been found to be the sole or major manifestation of NLRP3-AID. Here, we tested 110 autosomal dominant HL families with a custom panel of 237 HL genes and found one family carrying the c.

Searching for the Molecular Basis of Partial Deafness.

Hearing is an important human sense for communicating and connecting with others. Partial deafness (PD) is a common hearing problem, in which there is a down-sloping audiogram. In this study, we apply a practical system for classifying PD patients, used for treatment purposes, to distinguish two groups of patients: one with almost normal hearing thresholds at low frequencies (PDT-EC, = 20), and a second group with poorer thresholds at those same low frequencies (PDT-EAS, = 20).

Update on CD164 and LMX1A genes to strengthen their causative role in autosomal dominant hearing loss.

Novel hearing loss (HL) genes are constantly being discovered, and evidence from independent studies is essential to strengthen their position as causes of hereditary HL. To address this issue, we searched our genetic data of families with autosomal dominant HL (ADHL) who had been tested with high-throughput DNA sequencing methods. For CD164, only one pathogenic variant in one family has so far been reported.

Molecular Inversion Probe-Based Sequencing of Exons and Splice Sites as a Cost-Effective Screening Tool in USH2 and arRP Cases.

A substantial proportion of subjects with autosomal recessive retinitis pigmentosa (arRP) or Usher syndrome type II (USH2) lacks a genetic diagnosis due to incomplete screening in the early days of genetic testing. These cases lack eligibility for optimal genetic counseling and future therapy. defects are the most frequent cause of USH2 and are also causative in individuals with arRP.

TBC1D24 emerges as an important contributor to progressive postlingual dominant hearing loss.

Several TBC1D24 variants are causally involved in the development of profound, prelingual hearing loss (HL) and different epilepsy syndromes inherited in an autosomal recessive manner. Only two TBC1D24 pathogenic variants have been linked with postlingual progressive autosomal dominant HL (ADHL). To determine the role of TBC1D24 in the development of ADHL and to characterize the TBC1D24-related ADHL, clinical exome sequencing or targeted multigene (n = 237) panel were performed for probands (n = 102) from multigenerational ADHL families.

Functional Polymorphism of and as Potential Biomarker of Auditory Neuroplasticity in Prelingual Deafness Treatment With Cochlear Implantation-A Retrospective Cohort Analysis.

Genetic biomarkers of neuroplasticity in deaf children treated with cochlear implantation (CI) might facilitate their clinical management, especially giving them better chances of developing proficient spoken language. We investigated whether carrying certain variants of the genes encoding matrix metalloproteinase and neurotrophin brain-derived neurotrophic factor (), involved in synaptic plasticity, can be taken as prognostic markers of how well auditory skills might be acquired. Association analysis of functional rs3918242 and rs6265 variants and the child's auditory development measured at CI activation and 1, 5, 9, 14, and 24 months post CI activation with LittlEARS Questionnaire (LEAQ) was conducted in a group of 100 children diagnosed with DFNB1-related deafness, unilaterally implanted before the age of 2 years.

Complex Phenotypic Presentation of Syndromic Hearing Loss Deciphered as Three Separate Clinical Entities: How Genetic Testing Guides Final Diagnosis.

Background: Genetically determined prelingual hearing loss (HL) may occur in an isolated or syndromic form.

Objective: The aim of the study was to unravel the genetic cause of medical problems in a 21-year-old woman, whose phenotypic presentation extended beyond Stickler syndrome and included enlarged vestibular aqueduct (EVA) and persistent microhematuria.

Methods And Results: After sequencing of clinical exome, a known de novo COL2A1 pathogenic variant (c.

Analysis of major otosclerosis-associated variants in and genes in Polish patients.

Introduction: Otosclerosis (OTSC) is one of the most common causes of progressive adult-onset hearing loss in the Caucasian population, with a female preponderance. The etiology of OTSC is complex and there are a number of genetic variants reported to be associated with OTSC susceptibility, but no data on the genetic background of OTSC in patients originating from the central-eastern part of Europe have been available. The purpose of our study was to investigate in Polish patients the frequency of genetic variants previously reported to be most strongly associated with OTSC.

Two Novel Pathogenic Variants Confirm Causative Role in Perrault Syndrome with Renal Involvement.

(required for meiotic nuclear division 1 homolog) pathogenic variants are known to cause combined oxidative phosphorylation deficiency (COXPD11), a severe multisystem disorder. In one patient, a homozygous pathogenic variant, with an established role in COXPD11, was associated with a Perrault-like syndrome. We performed a thorough clinical investigation and applied a targeted multigene hearing loss panel to reveal the cause of hearing loss, ovarian dysfunction (two cardinal features of Perrault syndrome) and chronic kidney disease in two adult female siblings.

Effect of donor non-muscle myosin heavy chain (MYH9) gene polymorphisms on clinically relevant kidney allograft dysfunction.

Background: Despite its established association with chronic kidney disease (CKD) the role of myosin-9 (MYH9) gene variation on transplanted kidney function remains unknown. This study aimed at evaluating the effect of donor MYH9 nephrogenic variants on renal allograft function within the first post transplantation year.

Methods: In the longitudinal kidney transplant study 207 deceased donors were genotyped for previously known risk MYH9 single nucleotide polymorphisms (SNPs).

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist.

High expression of Matrix Gla Protein in Schnyder corneal dystrophy patients points to an active role of vitamin K in corneal health.

Purpose: Schnyder corneal dystrophy (SCD) is a rare autosomal dominant disorder characterized by corneal lipid accumulation and caused by UBIAD1 pathogenic variants. UBIAD1 encodes a vitamin K (VK) biosynthetic enzyme. To assess the corneal and vascular VK status in SCD patients, we focused on matrix Gla protein (MGP), a VK-dependent protein.