A5062116722- Hearing, Cochlea, Tinnitus, Genetics
- Congenital heart defects research
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Vestibular and auditory disorders
- Hereditary Neurological Disorders
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
- Connexins and lens biology
- CRISPR and Genetic Engineering
- Hearing Loss and Rehabilitation
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Cancer-related molecular mechanisms research
- Connective tissue disorders research
- Microbial infections and disease research
- Nonmelanoma Skin Cancer Studies
- Noise Effects and Management
- Single-cell and spatial transcriptomics
- Marine animal studies overview
- Veterinary Oncology Research
- Nasolacrimal Duct Obstruction Treatments
- Chromatin Remodeling and Cancer
- Animal Vocal Communication and Behavior
University of Miami
2014-2024
Dr. John T. Macdonald Foundation
2013-2024
Hospital for Sick Children
2015
Significance Concerted action of thousands proteins is required for the inner ear to convert acoustic waves into electrical signals hearing. Many these are currently unknown. This study uses a genetic approach identify FAM65B as gene mutated in family with sensorineural hearing loss. Characterization shows that it component plasma membrane stereocilia hair bundle, essential organelle which originate ear. Thus, previously unrecognized crucial
Significance The inner ear is a vertebrate organ of delicate and complex architecture that translates sound into electrical signals deciphered by the brain. This study utilizes genetic approach to associate mutation ROR1 (receptor tyrosine kinase-like orphan receptor 1) with anomalies deafness in humans. Characterization Ror1 mutant mice reveals fasciculation deficiencies spiral ganglion axons disruption sensory hair cell synapses peripheral innervations. molecular basis this phenotype...
Biallelic SORD mutations cause one of the most frequent forms recessive hereditary neuropathy, estimated to affect ∼10 000 patients in North America and Europe alone. Pathogenic loss-of-function changes encoded enzyme sorbitol dehydrogenase result abnormally high levels cells serum. How accumulation leads peripheral neuropathy remains be elucidated. A reproducible animal model for is essential illuminate pathogenesis deficiency preclinical studies potential therapies. Therefore, we have...
Molecular mechanisms governing the development of human cochlea remain largely unknown. Through genome sequencing, we identified a homozygous FOXF2 variant c.325A>T (p.I109F) in child with profound sensorineural hearing loss (SNHL) associated incomplete partition type I anomaly cochlea. This is not found public databases or over 1000 ethnicity-matched control individuals. I109 highly conserved residue forkhead box (Fox) domain FOXF2, member Fox protein family transcription factors that...
Deletions and mutations involving the Retinoic Acid Induced 1 (RAI1) gene at 17p11.2 cause Smith-Magenis syndrome (SMS). Here we report a patient with autism as main clinical presentation, some SMS-like features rare de novo RAI1 mutation, c.3440G > A (p.R1147Q). We functionally characterized p.R1147Q mutant protein. The located near nuclear localization signal, had no effect on subcellular of However, similar to previously reported missense in SMS patients, protein showed significant...
GATAD2B (GATA zinc finger domain containing 2B) variants are associated with the neurodevelopmental syndrome GAND, characterized by intellectual disability (ID), infantile hypotonia, apraxia of speech, epilepsy, macrocephaly and distinct facial features. encodes for a subunit Nucleosome Remodeling Histone Deacetylase (NuRD) complex. NuRD controls transcriptional programs critical proper neurodevelopment coupling histone deacetylase ATP-dependent chromatin remodeling activity. To study...
Geleophysic Dysplasia-1 (GD1) is an autosomal recessive disorder caused by ADAMTSL2 variants. It characterized distinctive facial features, limited joint mobility, short stature with brachydactyly, and the potential for life-threatening cardiovascular respiratory complications. The clinical spectrum spans from perinatal lethality to milder phenotypes in adult survivors, manifesting a heterogeneity. Adamtsl2–/– mouse model dies perinatally hinders further functional investigation. In this...
Molecular mechanisms governing the development of mammalian cochlea, hearing organ, remain largely unknown. Through genome sequencing in 3 subjects from 2 families with nonsyndromic cochlear aplasia, we identified homozygous 221-kb and 338-kb deletions a noncoding region on chromosome 8 an approximately 200-kb overlapping section. Genomic location deleted started 350 kb downstream GDF6, which codes for growth differentiation factor 6. Otic lineage cells differentiated induced pluripotent...
Abstract Background MBD5 , encoding the methyl-CpG-binding domain 5 protein, has been proposed as a necessary and sufficient driver of 2q23.1 microdeletion syndrome. De novo missense protein-truncating variants from exome sequencing studies have directly implicated in etiology autism spectrum disorder (ASD) related neurodevelopmental disorders (NDDs). However, little is known concerning specific function(s) MBD5. Methods To gain insight into complex interactions associated with alteration...
We have identified a
Background: Autism is characterized by difficulties in social interaction, communication, and repetitive behaviors; with different degrees of severity each the core areas. Haploinsufficiency point mutations RAI1 are associated Smith-Magenis syndrome (SMS), a genetic condition that scores within autism spectrum range for responsiveness neurobehavioral abnormalities, intellectual disability, developmental delay, sleep disturbance, self-injurious behaviors. Methods: To investigate relationship...
Abstract Potocki–Lupski syndrome (PTLS) is a genomic disorder associated with an ∼3 Mb duplication in 17p11.2. Clinical features include leanness, intellectual disability, autistic and developmental deficits. RAI1 gene dosage the PTLS phenotypes. To understand where when Rai1 overexpression detrimental, we generated mouse that over-expresses conditionally forebrain neurons (I-Rai1). Phenotypic characterization of I-Rai1 mice showed significant underweight, hyperactivity impaired learning...
Gastrointestinal adenocarcinomas are often reported in South American camelids (SAC). We describe here cases of gastroduodenal adenocarcinoma an adult alpaca ( Vicugna pacos) and a llama Llama glama); both SACs were anorectic lethargic before death. At autopsy, prominent firm caudal C3-pyloric-duodenal junction with stricture ulceration was present animals, as hemorrhages various organs hydrothorax. Microscopically, scattered nests, cords, tortuous acini neoplastic epithelial cells embedded...
SpringerPlus 2015, 4(Suppl 1):L1 MicroRNAs (miRNAs) are short, 22-25 nucleotide long transcripts that may suppress entire signaling pathways by interacting with the 3'-untranslated region (3'-UTR) of coding mRNA targets, interrupting translation and inducing degradation these targets.The 3'-UTRs brain compared to other tissues predict important roles for miRNAs.Supporting this notion, we found miRNAs co-evolved their target transcripts, non-coding pseudogenes miRNA recognition elements...
Abstract P2RX2 encodes the P2X2 receptor, which is an adenosine triphosphate (ATP) gated (purinoreceptor) ion channel. c. 178G > T (p.V60L) mutation was previously identified in two unrelated Chinese families, as cause of human DFNA41, a form dominant, early-onset and progressive sensorineural hearing loss. We generated characterized knock-in mouse model based on p.V60L that recapitulates phenotype. Heterozygous KI mice started to exhibit loss at 21-day-old progressed deafness by...
Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding hearing physiology its pathologies. Here we report on DNA variants in MINAR2 , encoding membrane integral NOTCH2-associated receptor 2, four families underlying autosomal recessive nonsyndromic deafness. Neurologic evaluation affected individuals at ages ranging from 4 80 y old does not show additional abnormalities. is a recently annotated gene with limited functional...
Hair cells (HCs) play crucial roles in perceiving sound, acceleration, and fluid motion. The tonotopic architecture of the sensory epithelium recognizes mechanical stimuli convert them into electrical signals. expression regulation genes inner ear is very important to keep organ functional. Our study first investigate role epigenetic reader Brd4 mouse ear. We demonstrate that HC specific deletion vivo sufficient cause profound hearing loss (HL), degeneration stereocilia, nerve fibers,...