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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 -
Molecular Genetics & Genomic Medicine Jun 2024Hearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment...
BACKGROUND
Hearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counselling for the patient's family.
METHODS
We detected and analysed 362 Chinese non-syndromic HL patients by screening of variants in 15 hot spot mutations. Subsequently, 40 patients underwent further whole-exome sequencing (WES) to determine genetic aetiology. The candidate variants were verified using Sanger sequencing. Twenty-three carrier couples with pathogenic variants or likely pathogenic variants chose to proceed with prenatal diagnosis using Sanger sequencing.
RESULTS
Among the 362 HL patients, 102 were assigned a molecular diagnosis with 52 different variants in 22 deafness genes. A total of 41 (11.33%) cases with the biallelic GJB2 (OMIM # 220290) gene mutations were detected, and 21 (5.80%) had biallelic SLC26A4 (OMIM # 605646) mutations. Mitochondrial gene (OMIM # 561000) mutations were detected in seven (1.93%) patients. Twenty of the variants in 15 deafness genes were novel. SOX10 (OMIM # 602229), MYO15A (OMIM # 602666) and WFS1 (OMIM # 606201) were each detected in two patients. Meanwhile, OSBPL2 (OMIM # 606731), RRM2B (OMIM # 604712), OTOG (OMIM # 604487), STRC (OMIM # 606440), PCDH15 (OMIM # 605514), LOXHD1 (OMIM # 613072), CDH23 (OMIM # 605516), TMC1 (OMIM # 606706), CHD7 (OMIM # 608892), DIAPH3 (OMIM # 614567), TBC1D24 (OMIM # 613577), TIMM8A (OMIM # 300356), PTPRQ (OMIM # 603317), SALL1 (OMIM # 602218), and GSDME (OMIM # 608798) were each detected in one patient. In addition, as regards one couple with a heterozygous variant of CDH23 and PCDH15, respectively, prenatal diagnosis results suggest that the foetus had double heterozygous (DH) variants of CDH23 and PCDH15, which has a high risk to cause ID/F type Usher syndrome.
CONCLUSION
Our study expanded the spectrum of deafness gene variation, which will contribute to the genetic diagnosis, prenatal diagnosis and the procreation guidance of deaf couple. In addition, the deafness caused by two genes should be paid attention to in the prenatal diagnosis of families with both deaf patients.
Topics: Humans; Female; Male; China; Mutation; Child; Hearing Loss; Adult; Child, Preschool; Sulfate Transporters; Adolescent; Cadherin Related Proteins
PubMed: 38860500
DOI: 10.1002/mgg3.2434 -
JCI Insight Jun 2024Human cytomegalovirus (HCMV) infection in infants infected in utero can lead to a variety of neurodevelopmental disorders. However, mechanisms underlying altered...
Human cytomegalovirus (HCMV) infection in infants infected in utero can lead to a variety of neurodevelopmental disorders. However, mechanisms underlying altered neurodevelopment in infected infants remain poorly understood. We have previously described a murine model of congenital HCMV infection in which murine CMV (MCMV) spreads hematogenously and establishes a focal infection in all regions of the brain of newborn mice, including the cerebellum. Infection resulted in disruption of cerebellar cortical development characterized by reduced cerebellar size and foliation. This disruption was associated with altered cell cycle progression of the granule cell precursors (GCPs), which are the progenitors that give rise to granule cells (GCs), the most abundant neurons in the cerebellum. In the current study, we have demonstrated that MCMV infection leads to prolonged GCP cell cycle, premature exit from the cell cycle, and reduced numbers of GCs resulting in cerebellar hypoplasia. Treatment with TNF-α neutralizing antibody partially normalized the cell cycle alterations of GCPs and altered cerebellar morphogenesis induced by MCMV infection. Collectively, our results argue that virus-induced inflammation altered the cell cycle of GCPs resulting in a reduced numbers of GCs and cerebellar cortical hypoplasia, thus providing a potential mechanism for altered neurodevelopment in fetuses infected with HCMV.
Topics: Animals; Cytomegalovirus Infections; Mice; Cerebellum; Cell Cycle; Disease Models, Animal; Female; Cytomegalovirus; Neural Stem Cells; Muromegalovirus; Animals, Newborn; Humans; Neurons; Tumor Necrosis Factor-alpha; Developmental Disabilities; Nervous System Malformations
PubMed: 38855871
DOI: 10.1172/jci.insight.175525 -
Cureus May 2024Researching Waardenburg syndrome (WS) underscores its rarity and complex symptomatology, presenting as a congenital disorder predominantly inherited in an autosomal...
Researching Waardenburg syndrome (WS) underscores its rarity and complex symptomatology, presenting as a congenital disorder predominantly inherited in an autosomal dominant pattern. It exhibits incomplete penetrance, which results in a wide range of clinical manifestations, with variable phenotypic presentations within the same family as well. The most commonly found features are facial abnormalities, hypopigmentation of the skin, heterochromia iridis, and conductive deafness. Adding to the eccentricities of this syndrome are its four subtypes, each presenting with its specific clinical features, which helps in delineating the subtype. A mutated paired box 3 () gene manifests as type 1 Waardenburg, which is characterized by sideways displacement of the inner angles of the eyes (i.e., dystopia canthorum), widely spaced eyes, congenital sensorineural hearing impairment, and patchy pigmentation of the iris, skin, and hair. Due to insufficient research, it has been difficult to isolate all the genetic mutations responsible for type 2, but its phenotype is very similar to type 1 with minor differences. Type 3 is characterized by musculoskeletal abnormalities. Waardenburg-Shah syndrome (type 4), which is associated with Hirschsprung disease, is the rarest subtype and is caused by genetic mutations in the endothelin receptor type B (), endothelin-3 (), or sex-determining region Y (SRY) box 10 () gene. We present a case series of this unique subtype that presented with a typical history of constipation due to Hirschsprung disease and had phenotypic manifestations of white forelock, heterochromia iridis, and bilateral sensorineural hearing loss (SNHL). In parallel with a positive 1° family history of a white forelock, we reflect on the fundamentals of this unique syndrome, as well as its management protocols, highlighting the importance of genetic counseling and cultivation of a high index of suspicion for its diagnosis.
PubMed: 38854277
DOI: 10.7759/cureus.59858