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Orphanet Journal of Rare Diseases Jun 2024Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous...
BACKGROUND
Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan.
RESULTS
In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference.
CONCLUSIONS
This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.
Topics: Adult; Female; Humans; Male; Middle Aged; Young Adult; Exons; Extracellular Matrix Proteins; Prevalence; Retinal Dystrophies; Taiwan; Usher Syndromes
PubMed: 38879497
DOI: 10.1186/s13023-024-03238-2 -
The Journal of Biological Chemistry Jun 2024Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np),...
Hearing, the ability to sense sounds, and the processing of auditory information are important for perception of the world. Mice lacking expression of neuroplastin (Np), a type-1 transmembrane glycoprotein, display deafness, multiple cognitive deficiencies, and reduced expression of plasma membrane calcium (Ca) ATPases (PMCAs) in cochlear hair cells and brain neurons. In this study, we transferred the deafness causing missense mutations pitch (C315S) and audio-1 (I122N) into human Np (hNp) constructs and investigated their effects at the molecular and cellular level. Computational molecular dynamics show that loss of the disulfide bridge in hNp causes structural destabilization of immunoglobulin-like domain (Ig) III and that the novel asparagine in hNp results in steric constraints and an additional N-glycosylation site in IgII. Additional N-glycosylation of hNp was confirmed by PNGaseF treatment. In comparison to hNp, transfection of hNp and hNp into HEK293T cells resulted in normal mRNA levels but reduced the Np protein levels and their cell surface expression due to proteasomal/lysosomal degradation. Furthermore, hNp and hNp failed to promote exogenous PMCA levels in HEK293T cells. In hippocampal neurons, expression of additional hNp or hNp was less efficient than hNp to elevate endogenous PMCA levels and to accelerate the restoration of basal Ca levels after electrically-evoked Ca transients. We propose that mutations leading to pathological Np variants, as exemplified here by the deafness causing Np mutants, can affect Np-dependent Ca regulatory mechanisms and may potentially cause intellectual and cognitive deficits in humans.
PubMed: 38879011
DOI: 10.1016/j.jbc.2024.107474 -
Medicine Jun 2024To explore the effects of focused solution nursing combined with cognitive intervention combined with functional training on negative emotions, compliance and quality of...
Focus on the effect of nursing care combined with cognitive intervention and functional training on negative emotion, compliance and quality of life in elderly patients with sudden deafness: A retrospective study.
To explore the effects of focused solution nursing combined with cognitive intervention combined with functional training on negative emotions, compliance and quality of life in elderly patients with sudden deafness. A total of 160 patients with sudden deafness in the elderly who were treated in our hospital from January 2019 to May 2021 were selected as the objects of this retrospective study. Based on different treatment approaches, subjects were divided into a control group and an observation group. Due to reasons such as the COVID-19 pandemic and transfers, 10 cases were lost to follow-up. In total, 75 cases were ultimately lost from both the control and observation groups. The control group implements cognitive intervention and functional training, and the observation group adopts focused solution nursing care on the basis of the control group. Observe and compare the effects of negative emotions, psychological distress, air conduction threshold level, compliance and quality of life of the 2 groups of patients. The air conduction hearing threshold level of the 2 groups of patients after nursing was lower than that before nursing and the observation group was lower than the control group. The positive coping scores of the 2 groups were significantly increased, and the negative coping scores were both significantly reduced and the observation group was in the 2 indicators. The degree of change was greater than that of the control group (P < .05). After nursing, the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of the observation group were lower than those of the control group (P < .05). The mental vitality score, social interaction score, emotional restriction score, and mental status of the observation group were significantly higher than those of the control group. The observation group's psychological compliance, activity compliance, dietary compliance, and treatment protocol compliance were significantly higher than those of the control group (P < .05). Adopting the focused solution model of nursing care can provide a better nursing recovery for elderly patients with sudden deafness, significantly improve the patient quality of life and anxiety and depression, improve patient compliance with treatment, and provide a certain reference for the nursing of elderly patients with sudden deafness.
Topics: Humans; Quality of Life; Retrospective Studies; Male; Female; Aged; Hearing Loss, Sudden; Patient Compliance; COVID-19; Emotions; Cognitive Behavioral Therapy; Aged, 80 and over; Adaptation, Psychological
PubMed: 38875427
DOI: 10.1097/MD.0000000000038283 -
Nature Communications Jun 2024Language and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores...
Language and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores alone. Here we aim to identify early-age brain alterations in autism that are prognostic of future language ability. Leveraging 372 longitudinal structural MRI scans from 166 autistic toddlers and 109 typical toddlers and controlling for brain size, we find that, compared to typical toddlers, autistic toddlers show differentially larger or thicker temporal and fusiform regions; smaller or thinner inferior frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most differences are replicated in an independent cohort of 75 toddlers. These brain alterations improve accuracy for predicting language outcome at 6-month follow-up beyond intake clinical and demographic variables. Temporal, fusiform, and inferior frontal alterations are related to autism symptom severity and cognitive impairments at early intake ages. Among autistic toddlers, brain alterations in social, language and face processing areas enhance the prediction of the child's future language ability.
Topics: Humans; Male; Female; Child, Preschool; Magnetic Resonance Imaging; Brain; Autistic Disorder; Infant; Language; Language Development
PubMed: 38871689
DOI: 10.1038/s41467-024-48952-4 -
The International Journal of... Jun 2024Mutations in the gene encoding Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) protein are associated with a variety of neurological disorders, ranging from...
Mutations in the gene encoding Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) protein are associated with a variety of neurological disorders, ranging from non-syndromic hearing loss to drug-resistant lethal epileptic encephalopathy and DOORS syndrome [Deafness, Onychodystrophy, Osteodystrophy, intellectual disability (formerly referred to as mental Retardation), and Seizures]. TBC1D24 is a vesicle-associated protein involved in neural crest cell and neuronal migration, maturation, and neurotransmission. In the cochlea, TBC1D24 has been detected in auditory neurons, but few reliable and convergent data exist about the sensory epithelium. Here, the expression of TBC1D24 has been characterized via immunolabelling throughout the postnatal maturation of the mouse cochlear sensory epithelium. TBC1D24 was detected in glia-like non-sensory epithelial cells during early developmental stages. In contrast, TBC1D24 was virtually absent in adjacent sensory hair cells. This expression distinguishing non-sensory from sensory epithelial cells almost disappears around the onset of hearing. Until now, TBC1D24 was mainly described as a neuronal protein either in the brain or in the cochlea. The present observations suggest that TBC1D24 could also regulate vesicle trafficking in cochlear glia-like non-sensory epithelial cells. For a long time, research about epilepsy has been mainly neurocentric. However, there is now evidence proving that glial cell dysregulation contribute to pathogenesis of epilepsy and neurodevelopmental disorders. As a consequence, exploring the possibility that TBC1D24 could also have a role in glial cells of the central nervous system could help to gain insight into TBC1D24-related neurological pathogenesis.
PubMed: 38869222
DOI: 10.1387/ijdb.240060jd -
Croatian Medical Journal Jun 2024To determine the spectrum and frequency of disease-causing variants in patients with non-syndromic hearing loss (NSHL) and to investigate the diagnostic yield of the...
AIM
To determine the spectrum and frequency of disease-causing variants in patients with non-syndromic hearing loss (NSHL) and to investigate the diagnostic yield of the applied genetic methods.
METHODS
The study enrolled 306 unrelated patients with childhood-onset, mild-to-profound NSHL referred to Children's Hospital Zagreb for genetic testing between March 2006 and October 2023. The GJB2 variants were analyzed with the multiplex ligation-dependent probe amplification method and Sanger sequencing of the coding region of the GJB2 gene. In 21 patients negative for GJB2 biallelic variants, clinical exome sequencing (CES) was performed.
RESULTS
Among 234 disease-associated GJB2 alleles detected, 19 were clinically relevant, of which 18 were reported as pathogenic/likely pathogenic. The c.35delG variant accounted for 73.5% of the mutated alleles. More than half of the patients with biallelic GJB2 variants (64/110, 58.2%) were 35delG homozygotes. Seventeen non-GJB2 variants were found in 10 genes (TECTA, NOG, SLC26A4, PCDH15, TMPRSS3, USH2A, GATA3, MYO15A, SOX10, COL2A1) in 11 participants, and 5 variants (in TECTA, NOG, PCDH15, and SOX10) were novel (29.4%).
CONCLUSION
We were able to elucidate the genetic cause of hearing loss in 121 patients, with an overall diagnostic rate of 39.5%. The c.35delG was the most common variant. CES allowed us to diagnose almost half of the patients with HL; to distinguish NSHL from the syndromic form of HL in cases where the phenotype was unclear or where symptoms were absent from an early age; and to discover novel variants.
Topics: Humans; Croatia; Child; Connexin 26; Female; Male; Child, Preschool; Adolescent; Infant; Genetic Testing; Genetic Variation; Connexins; Mutation; Exome Sequencing; Hearing Loss; Alleles; Young Adult; Deafness
PubMed: 38868966
DOI: 10.3325/cmj.2024.65.198 -
BMC Geriatrics Jun 2024Hearing loss is common in aging adults and is an important public health concern. Self-reported measures of hearing difficulty are often used in research and clinical...
BACKGROUND
Hearing loss is common in aging adults and is an important public health concern. Self-reported measures of hearing difficulty are often used in research and clinical practice, as they capture the functional impacts of hearing loss on individuals. However, little research has evaluated the prevalence or factors associated with self-reported hearing difficulty. Therefore, the purpose of this study was to determine the prevalence of self-reported hearing difficulty, measured by the Revised Hearing Handicap Inventory (RHHI), and associated factors.
METHODS
This study was conducted in a community-based cohort study based in Charleston, SC. We determined the prevalence of RHHI self-reported hearing difficulty (score ≥ 6 points) and evaluated associated factors with logistic regression models. Results are presented as odds ratios (OR) with corresponding 95% confidence intervals (95% CI).
RESULTS
There were 1558 participants included in this study (mean age 63.7 [SD 14.4], 56.9% female, 20.0% Minority race). The prevalence of RHHI self-reported hearing difficulty was 48.8%. In a multivariable model, older age (per + 1 year; OR 0.97 [95% CI 0.96, 0.98]), Minority (vs. White) race (OR 0.68 [95% CI 0.49, 0.94]), and speech-in-noise scores that are better than predicted (OR 0.99 [95% CI 0.98, 1.00]) were associated with lower odds of RHHI self-reported hearing difficulty. Furthermore, female (vs. male) sex (OR 1.39 [95% CI 1.03, 1.86]), higher PTA in the worse ear (per + 1 dB; OR 1.10 [95% CI 1.09, 1.12]), more comorbid conditions (vs. 0; 1 condition: OR 1.50 [95% CI 1.07, 2.11]; 2 conditions: OR 1.96 [95% CI 1.32, 2.93]; 3 + conditions: OR 3.00 [95% CI 1.60, 5.62]), noise exposure (OR 1.54 [95% CI 1.16, 2.03]), bothersome tinnitus (OR 2.16 [95% CI 1.59, 2.93]), and more depressive symptoms (OR 1.04 [95% CI 1.01, 1.07]) were associated with higher odds of RHHI self-reported hearing difficulty.
CONCLUSIONS
The prevalence of RHHI self-reported hearing difficulty is high, and associated factors included demographics, audiometric hearing and other hearing-related factors, and physical and mental health. The RHHI likely captures functional impacts of hearing loss that are not captured by audiometry alone. Study findings can support the correct interpretation of the RHHI in research and clinical settings.
Topics: Humans; Male; Female; Middle Aged; Self Report; Hearing Loss; Prevalence; Aged; Cohort Studies; Disability Evaluation; Adult; Aged, 80 and over
PubMed: 38867166
DOI: 10.1186/s12877-024-04901-w -
BMC Ophthalmology Jun 2024Refractive errors, amblyopia, strabismus, and low vision are more common among children with hearing impairments in comparison with their hearing peers. Neglecting...
BACKGROUND AND AIM
Refractive errors, amblyopia, strabismus, and low vision are more common among children with hearing impairments in comparison with their hearing peers. Neglecting visual disorders can pose educational and social problems for these children. The present study aimed to assess the prevalence of refractive errors, amblyopia, strabismus, and low vision among hearing-impaired and deaf students in Kermanshah.
MATERIALS AND METHODS
A total of 79 deaf and hearing impaired students within the age range of 7-20 years (mean age of 15.01 ± 2.72) underwent optometric examinations, including autorefractometry, retinoscopy, ophthalmoscopy, slit lamp, visual acuity measurement, and cover-uncover test. Those who needed further evaluation were referred to the Ophthalmology Clinic of Imam Khomeini Hospital.
RESULTS
Regarding the prevalence of refractive errors, 32 (40.5%) subjects had one or a combination of refractive errors, the most common of which was astigmatism (36.7%), followed by amblyopia (15.1%). The most common type of strabismus was latent strabismus (heterophoria) (88.6%), followed by exophoria (81%). Moreover, 3 (3.7%) cases had nystagmus. A significant difference was observed between the prevalence of amblyopia and the degree of hearing loss (P = 0.026), and no significant difference was detected in other cases.
CONCLUSION
As evidenced by the obtained results, refractive errors, amblyopia, strabismus, and low vision are more prevalent among deaf and hearing-impaired children compared to normal children because deaf and hearing-impaired children are not able to convey their vision problems and need to compensate for their poor hearing with an enhanced sense of sight, inattention to these disorders can present these children with serious educational and social problems. Therefore, eye screening examinations are of paramount importance in deaf and hearing-impaired children.
Topics: Humans; Strabismus; Child; Adolescent; Male; Female; Refractive Errors; Vision, Low; Amblyopia; Prevalence; Young Adult; Visual Acuity; Iran; Cross-Sectional Studies; Persons With Hearing Impairments; Deafness; Students
PubMed: 38867144
DOI: 10.1186/s12886-024-03515-5 -
Orphanet Journal of Rare Diseases Jun 2024The present study aimed to test the hypothesis stating that the cognitive potential of individuals with deafblindness is equal to those without a deafblind condition, an...
BACKGROUND
The present study aimed to test the hypothesis stating that the cognitive potential of individuals with deafblindness is equal to those without a deafblind condition, an assumption that until now has been empirically unsubstantiated within the field of deafblindness.
METHODS
To explore the assumption, 15 children and adolescents with CHARGE underwent cognitive assessment with WISC-V using a sequential two-level assessment design. The 1st level involved standardized test conditions. The 2nd level was designed as a continuation of the performances obtained from the 1st level and involved accommodations to compensate for sensory motor impairment. Statistical procedures involved the sample as a whole and when divided into two subgroups: (i) participants with CHARGE without deafblindness; (ii) participants with CHARGE and deafblindness using the 1st level scores as base line.
RESULTS
Although results showed significantly lower scores in the deafblind subgroup with standardized procedures, they approximated the others after accommodating for their sensory deficits. This positive increase proved significant.
CONCLUSION
Findings supported the assumption of equal cognitive potential of individuals with and without deafblindness. Results indicated that the children and adolescents with deafblindness had most effect of the accommodations, enabling them to approximate the results of the subgroup without deafblindness. These gains were attributed enhanced accessibility endorsed by the accommodations and represented the participants latent cognitive dispositions only realized under certain circumstances.
Topics: Humans; Adolescent; Child; Female; Male; Deaf-Blind Disorders; Cognition; CHARGE Syndrome
PubMed: 38863011
DOI: 10.1186/s13023-024-03222-w -
Communications Biology Jun 2024Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different...
Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior.
Topics: Humans; Aphasia; Female; Male; Middle Aged; Aged; Brain; Aging, Premature; Magnetic Resonance Imaging; Stroke; Aging; Severity of Illness Index; Gray Matter; Adult
PubMed: 38862747
DOI: 10.1038/s42003-024-06211-8