A5035603589- Hearing, Cochlea, Tinnitus, Genetics
- RNA regulation and disease
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Hearing Loss and Rehabilitation
- Cellular transport and secretion
- RNA modifications and cancer
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Ear Surgery and Otitis Media
- Developmental Biology and Gene Regulation
- Endoplasmic Reticulum Stress and Disease
- Galectins and Cancer Biology
- Connexins and lens biology
- Erythrocyte Function and Pathophysiology
- Retinoids in leukemia and cellular processes
- Genetic Neurodegenerative Diseases
- Microbial Metabolism and Applications
- Fetal and Pediatric Neurological Disorders
- Connective tissue disorders research
- Hedgehog Signaling Pathway Studies
- Lysosomal Storage Disorders Research
- interferon and immune responses
Columbia University Irving Medical Center
2020-2025
Madras Medical College
1993
Age-related (AR) hearing loss (HL) is the most prevalent sensorineural disorder in older adults. Here we demonstrate that rare-variants well-established Mendelian HL genes play an important role ARHL etiology. In all identified 32 which are associated with ARHL. We performed single and rare-variant aggregate association analyses using exome data obtained from white-Europeans self-reported phenotypes UK Biobank. Our analysis revealed previously unreported associations between non-syndromic...
Congenital hearing impairment is a sensory disorder that genetically highly heterogeneous. By performing exome sequencing in two families with congenital nonsyndromic profound sensorineural loss (SNHL), we identified autosomal dominantly inherited missense variants [p.(Asn283Ser); p.(Thr116Ile)] GREB1L, neural crest regulatory molecule. The p.(Thr116Ile) variant was also associated bilateral cochlear aplasia and nerve upon temporal bone imaging, an ultra-rare phenotype previously seen...
To investigate the diagnostic value of implementing a stepwise genetic testing strategy (SGTS) in genetically unsolved cases with dystrophinopathies.After routine 872 male patients highly suspected dystrophinopathies, we identified 715 pathogenic DMD variant. Of 157 who had no variants and underwent muscle biopsy, 142 were confirmed to have other myopathies, 15 dystrophinopathies remained undiagnosed. These more comprehensive evaluation as part SGTS pipeline, which included analysis...
Dystrophic epidermolysis bullosa is a rare subtype of inherited bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated Pakistani family dystrophic via exome sequencing identified pathogenic nonsense variant COL7A1 NM_000094 c.1573 C > T:p.(Arg525*). The pattern observed was consistent semi-dominant model, where heterozygous parents exhibited mild...
ABSTRACT To elucidate the genetic etiology of hearing impairment (HI) in South Africa, 45 nonsyndromic HI (NSHI) and syndromic (SHI) families with ≥ 2 affected members were analyzed. Exome sanger sequencing used to identify causal genes. For NSHI, 14 24 segregated variants NSHI genes, that is, CDH23 , GJB2 MITF MYO7A, MYO15A PCDH15 POU3F4 REST SLC26A4 TMPRSS3 WFS1 . 21 SHI families, have Waardenburg syndrome, two Branchio‐Oto‐Renal syndromes, one each Bartter, Chudley‐McCullough,...
We investigated hearing impairment (HI) in 51 families from Ghana with at least two affected members that were negative for GJB2 pathogenic variants. DNA samples 184 family underwent whole-exome sequencing (WES). Variants found 14 known non-syndromic HI (NSHI) genes [26/51 (51.0%) families], five can underlie either syndromic or NSHI [13/51 (25.5%)], and one gene [1/51 (2.0%)]. CDH23 MYO15A contributed the most to [31.4% (16/51 families)]. For DSPP, an autosomal recessive mode of inheritance...
Congenital hearing impairment (HI) is genetically heterogeneous making its genetic diagnosis challenging. Investigation of novel HI genes and variants will enhance our understanding the molecular mechanisms to aid diagnosis. We performed exome sequencing analysis using DNA samples from affected members two large families Ghana Pakistan, segregating autosomal-dominant (AD) non-syndromic (NSHI). Using in silico approaches, we modeled evaluated effect likely pathogenic on protein structure...
Abstract Although variant alleles of hundreds genes are associated with sensorineural deafness in children, the and involved remain largely unknown Sub-Saharan regions Africa. We ascertained 56 small families mainly Yoruba ethno-lingual ancestry or near Ibadan, Nigeria, that had at least one individual nonsyndromic, severe-to-profound, prelingual-onset, bilateral hearing loss not attributed to nongenetic factors. performed a combination exome Sanger sequencing analyses evaluate both nuclear...
Approximately half of congenital hearing impairment cases are inherited, with non-syndromic (NSHI) being the most frequent clinical entity genetic cases. A family from Cameroon NSHI was investigated by performing exome sequencing using DNA samples obtained three members, followed direct Sanger in additional members and controls participants. We identified an autosomal dominantly inherited novel missense variant [NM_001174116.2:c.918G>T; p.(Q306H)] DMXL2 gene (MIM:612186) that...
Hearing impairment (HI) is a common disorder of sensorineural function with highly heterogeneous genetic background. Although substantial progress has been made in the understanding etiology hereditary HI, many genes implicated HI remain undiscovered. Via exome and Sanger sequencing DNA samples obtained from consanguineous Pakistani families that segregate profound prelingual we identified rare homozygous missense variants four (ADAMTS1, MPDZ, MVD, SEZ6) are likely underlying cause HI....
Atypical Gaucher disease is caused by variants in the PSAP gene. Saposin C one of four homologous proteins derived from sequential cleavage saposin precursor protein, prosaposin. It an essential activator for glucocerebrosidase, which deficient disease. Although atypical due to deficiency rare, it exhibits vast phenotypic heterogeneity. Here, we report on a Pakistani family that features disease, i.e., prelingual profound sensorineural hearing impairment, vestibular dysfunction,...
DNA samples from five members of a multiplex non-consanguineous Cameroonian family, segregating prelingual and progressive autosomal recessive non-syndromic sensorineural hearing impairment, underwent whole exome sequencing. We identified novel bi-allelic compound heterozygous pathogenic variants in CLIC5. The identified, i.e., the missense [NM_016929.5:c.224T>C; p.(L75P)] splicing (NM_016929.5:c.63+1G>A), were validated using Sanger sequencing all seven available family co-segregated...
Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder which clinically and genetically heterogeneous. Genome sequencing identified biallelic
Hearing impairment (HI) is the most common neurosensory disorder globally and reported to be more prevalent in low-income countries. In high-income countries, up 50% of congenital childhood HI genetic origin. However, there limited data on from sub-Saharan African populations. this study, we investigated causes Malian populations, using whole exome sequencing. Furthermore, cDNA was transfected into HEK293T cells for localisation expression analysis a candidate gene. Twenty-four multiplex...
Hearing impairment (HI) is a sensory disorder with prevalence of 0.0055 live births in South Africa. DNA samples from African family presenting progressive, autosomal dominant non-syndromic HI were subjected to whole-exome sequencing, and novel monoallelic variant REST [c.1244GC; p.(C415S)], was identified as the putative causative variant. The co-segregation confirmed Sanger Sequencing. absent databases, 103 healthy controls, 52 probands isolated HI. In silico analysis indicates that...
Abstract Background Childhood hearing impairment (HI) is genetically heterogeneous with many implicated genes, however, only a few of these genes are reported in African populations. Methods This study used exome and Sanger sequencing to resolve the possible genetic cause non-syndromic HI Ghanaian family. Results We identified novel variant c.3041G > A: p.(Gly1014Glu) GREB1L (DFNA80) index case. The : had CADD score 26.5 was absent from human genomic databases such as TopMed gnomAD. In...
Wolfram syndrome (WFS) is characterized by deafness, diabetes mellitus, and insipidus along with optic atrophy. WFS has an autosomal recessive mode of inheritance due to variants in WFS1 CISD2.We evaluated the underlying molecular etiology three affected members a consanguineous family hearing impairment, bicuspid aortic valve, mellitus insipidus, clinodactyly, gastrointestinal tract abnormalities via exome sequencing approach. We correlated clinical imaging data genetic findings their...
Abstract Bilateral perisylvian polymicrogyria (BPP) is a structural malformation of the cerebral cortex that can be caused by several genetic abnormalities. The most common clinical manifestations BPP include intellectual disability and epilepsy. Cytoplasmic FMRP‐interacting protein 2 (CYFIP2) interacts with fragile X mental retardation (FMRP). CYFIP2 variants cause various brain abnormalities disability, epileptic encephalopathy dysmorphic features. We present girl multiple disabilities...
Abstract Bilateral perisylvian polymicrogyria is the most common form of regional within malformations cortical development, constituting 20% all development. characterized by an excessive folding cerebral cortex and abnormal layering. Notable clinical features include upper motoneuron dysfunction, dysarthria asymmetric quadriparesis. Cognitive impairment epilepsy are frequently observed. To identify genetic variants underlying bilateral in Finland, we examined 21 families using standard...