A5003881844- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Ear Surgery and Otitis Media
- RNA regulation and disease
- Vestibular and auditory disorders
- Congenital heart defects research
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Tumors and Oncological Cases
- Viral-associated cancers and disorders
- Sinusitis and nasal conditions
- Acoustic Wave Phenomena Research
- Ear and Head Tumors
- Biochemical Analysis and Sensing Techniques
- Genetic and rare skin diseases.
- Soft tissue tumor case studies
- Cerebral Venous Sinus Thrombosis
- Autoimmune and Inflammatory Disorders Research
- Traumatic Brain Injury Research
- Noise Effects and Management
- Systemic Lupus Erythematosus Research
- Gene expression and cancer classification
- Reconstructive Facial Surgery Techniques
Boston Children's Hospital
2021-2025
Harvard University
2021-2025
Boston University
2021-2024
Lemuel Shattuck Hospital
2023
University of Iowa Hospitals and Clinics
2015-2019
University of Iowa
2010-2019
Hearing loss is the most common sensory deficit in humans, affecting 1 500 newborns. Due to its genetic heterogeneity, comprehensive diagnostic testing has not previously been completed a large multiethnic cohort. To determine aggregate contribution inheritance makes non-syndromic hearing loss, we performed clinical with targeted genomic enrichment and massively parallel sequencing on 1119 sequentially accrued patients. No patient was excluded based phenotype, or previous testing. Testing...
The classification of genetic variants represents a major challenge in the post-genome era by virtue their extraordinary number and complexities associated with ascribing clinical impact, especially for disorders exhibiting exceptional phenotypic, genetic, allelic heterogeneity. To address this hearing loss, we have developed Deafness Variation Database (DVD), comprehensive, open-access resource that integrates all available genomic, data together expert curation to generate single each...
ABSTRACT Kleefstra syndrome (KLEFS) is a genetic neurodevelopmental disorder caused by haploinsufficiency of EHMT1 . The full spectrum clinical features and genotype–phenotype correlations currently not fully understood. We performed retrospective chart review patients with KLEFS evaluated at the Boston Children's Hospital Clinic. There were 65 individuals (40 females, 25 males, mean age 9.3 years). 17% had large 9q34 deletions (≥ 1 Mb), 29% small (< 54% sequence variants. Global...
Early intervention for newborns who are deaf or hard-of-hearing leads to improved language, communication, and social-emotional outcomes. Universal physiologic newborn hearing screening has been widely implemented across the United States with goal of identifying hard-of-hearing, thereby reducing time diagnosis intervention. The current screen is generally successful in accomplishing its goals but improvements could be made. In past ten years, genetic testing emerged as most important...
Objective Posttransplant lymphoproliferative disorder (PTLD) is a complication of pediatric solid organ transplantation. Benign adenotonsillar lymphoid hyperplasia confounds the ability to diagnose PTLD. Our aim was identify factors that predict presence PTLD inform decision‐making regarding adenotonsillectomy. Methods The electronic medical records at quaternary children's hospital were queried over 23‐year period (2000–2023) for transplant patients underwent tonsillectomy and/or...
We report on a secreted protein found in mammalian cochlear outer hair cells (OHC) that is member of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family proteins. Ceacam16 mRNA expressed OHC, and its product localizes to tips tallest stereocilia tectorial membrane (TM). This specific localization suggests role maintaining integrity TM as well connection between OHC TM, linkage essential for mechanical amplification. In agreement with this role, CEACAM16 colocalizes...
The prevalence of DFNA8/DFNA12 (DFNA8/12), a type autosomal dominant nonsyndromic hearing loss (ADNSHL), is unknown as comprehensive population-based genetic screening has not been conducted. We therefore completed unbiased for TECTA mutations in Spanish cohort 372 probands from ADNSHL families. Three additional families (Spanish, Belgian, and English) known to be linked DFNA8/12 were also included the screening. In an 835 American families, we preselected 73 based on audiometric data....
We studied a consanguineous Palestinian Arab family segregating an autosomal recessive progressive myoclonus epilepsy (PME) with early ataxia. PME is rare, often fatal syndrome, initially responsive to antiepileptic drugs which over time becomes refractory and can be associated cognitive decline. Linkage analysis was performed the disease locus narrowed chromosome 19p13.3. Fourteen candidate genes were screened by conventional Sanger sequencing in one, LMNB2, novel homozygous missense...
Objectives Genetic testing is the standard‐of‐care for diagnostic evaluation of bilateral, symmetric, sensorineural hearing loss (HL). We sought to determine efficacy a comprehensive genetic method, exome sequencing (ES), in heterogeneous pediatric patient population with bilateral asymmetric, and unilateral HL. Methods Trio‐based ES was performed patients confirmed HL including those Results completed 218 probands. A cause identified 31.2% probands ( n = 68). The rate 40.7% HL, 23.1%...
Abstract Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number individuals who remain without diagnosis after even most advanced genetic testing. PKHD1L1 was established as necessary for formation cochlear hair-cell stereociliary coat and causes in mice zebrafish when mutated. We sought to determine if biallelic variants also cause humans. Exome sequencing performed on DNA four families segregating autosomal recessive...
Understanding genetic causes of hearing loss can determine the pattern and course a patient’s may also predict outcomes after cochlear implantation. Our goal in this study was to evaluate large cohort adults children with implants. We performed comprehensive testing on all patients undergoing Of 459 included study, 128 (28%) had positive testing. In total, 44 genes were identified as causative. The top 5 implicated GJB2 (20, 16%), TMPRSS3 (13, 10%), SLC26A4 (10, 8%), MYO7A (9, 7%), MT‐RNR1...
Usher syndrome (USH), the most common form of deaf-blindness, displays extensive genetic, allelic, and phenotypic heterogeneity. The dual sensory impairment associated with this disorder makes an important target for gene therapy, dozens published preclinical studies targeting multiple USH genes using therapy strategies. Nine have been conclusively linked to syndrome; however, data on prevalence contribution specific genetic variants is lacking. Such information essential choosing a...
Objective Disordered T peripheral helper (Tph)‐B cell interactions have been implicated in several forms of inflammatory arthritis, including oligoarticular juvenile idiopathic arthritis (oligo JIA). We sought to evaluate the Tph‐B axis oligo JIA through an analysis intra‐articular B cells. Methods cells from blood and synovial fluid (SF) 44 children with were compared those tonsils controls. Flow cytometry, receptor (BCR) repertoire analysis, autoantibody profiling used characterize Results...
ABSTRACT Usher syndrome, the most common form of deaf‐blindness, displays extensive genetic, allelic, and phenotypic heterogeneity. The dual sensory impairment associated with this autosomal recessive disorder makes syndrome an important target for gene therapy, dozens published preclinical studies targeting multiple genes using therapy strategies. Nine have been conclusively linked to syndrome; however, data on prevalence contribution specific genetic variants is lacking. Such information...
Autosomal dominant nonsyndromic hearing loss (ADNSHL) is a common and often progressive sensory deficit. ADNSHL displays high degree of genetic heterogeneity varying rates progression. Accurate, comprehensive, cost-effective testing facilitates counseling provides valuable prognostic information to affected individuals. In this article, we describe the algorithm underlying AudioGene, software system employing machine-learning techniques that utilizes phenotypic derived from audiograms...
Copy number variations (CNVs), a major cause of genetic hearing loss, most frequently involve the STRC gene, located on chr15q15.3 and causally related to autosomal recessive non-syndromic loss (ARNSHL) at DFNB16 locus. The interpretation sequence data can be challenging due existence virtually identical pseudogene, pSTRC, that promotes complex genomic rearrangements in this region. Targeted enrichment with massively parallel sequencing (TGE+MPS) has emerged as preferred method by which...
Cochlear implantation, a surgical method to bypass cochlear hair cells and directly stimulate the spiral ganglion, is standard treatment for severe-to-profound hearing loss. Changes in implant electrode array design approach now allow preservation of acoustic implanted ear. Electrocochleography (ECochG) was performed eight subjects assess cell neural function elucidate underlying genetic Three had pathogenic variants TMPRSS3 five genes known affect sensory partition. The mechanism by which...
Dizziness after concussion is primarily attributed to effects on the brain, but traumatic inner ear disorders can also contribute. Benign paroxysmal positional vertigo (BPPV) a common vestibular disorder that result from minor head trauma and be easily diagnosed rapidly treated in an office setting. The role of BPPV pediatric postconcussive dizziness has not been well-studied.To evaluate prevalence clinical features group patients with prolonged concussion.Case-control study.Level...
Abstract Boston Children’s Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Rare Disease Collaborative (CRDC), hospital offers CLIA-grade exome genome sequencing, along with other types, patients enrolled in specialized studies. The data, consented broad use, are harmonized analyzed CRDC-supported variant interpretation tools. Since its launch, 66 investigators representing 26 divisions 45...