Publications by authors named "Guney Bademci"

encodes a kinesin motor protein associated with isolated congenital fibrosis of the extraocular muscles (CFEOM), which occurs when the autoinhibitory interaction between its motor and third coiled-coil domains is disrupted. In this study, we describe a female child who is heterozygous for a novel de novo missense variant in p.Leu664Pro, located in the second coiled-coil domain that was absent in her unaffected parents and in healthy population cohorts.

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To determine the genetic causes of sensorineural hearing loss (SNHL) associated with inner ear anomalies, 11 unrelated Turkish individuals diagnosed with SNHL and an inner ear anomaly using temporal bone computed tomography and inner ear magnetic resonance imaging underwent exome or whole genome sequencing to identify underlying genetic defects. None of the individuals was diagnosed with a recognized syndrome. Four of the 11 probands were homozygous for variants, , , , and .

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  • ATP1A1 gene is linked to neurological diseases and encodes a sodium-potassium ATPase.
  • Researchers identified a specific variant, NM_000701.8: c.2707G>A;p.(Gly903Arg), in two children with developmental delays and autism, which was not present in healthy controls.
  • Experimental testing showed that this variant reduces cell viability, indicating a loss of function and confirming its pathogenic role in expanding the known effects of ATP1A1 mutations.
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  • SNURPORTIN-1 (SNUPN) is important for transporting proteins in the cell but its exact job wasn’t known before.
  • Researchers studied 18 kids with a rare type of muscular dystrophy and found that changes in the SNUPN gene might be causing their health issues.
  • The study showed that the faulty SNUPN protein doesn't work properly, leading to problems in muscle cells and causing symptoms of muscular dystrophy in these kids.
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  • Hearing loss (HL) can be caused by variations in over 200 genes, but many families still don't receive a clear genetic diagnosis despite extensive testing.
  • In a study involving families with severe to profound, non-syndromic bilateral sensorineural HL, researchers used advanced genetic sequencing techniques to uncover the complexity of multiple gene variants contributing to HL in family members.
  • One novel finding included a variant in the TOGARAM2 gene, suggesting it could be linked to autosomal recessive non-syndromic HL, highlighting the importance of analyzing each affected individual to identify both known and potential new HL-related genes.
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  • - Autosomal dominant sensorineural hearing loss (ADSNHL) is caused by genetic variations, particularly in the MYH14 gene, which complicates the understanding of these variants' effects due to inconsistent expression and limited family studies.* - In a recent study involving exome sequencing of six unrelated ADSNHL families, five MYH14 variants were identified, including three that had not been reported before, with two classified as likely pathogenic.* - Computational modeling indicates that these novel variants could impact protein stability and interactions, highlighting the potential role of MYH14 in severe nonsyndromic hearing loss, though more research is needed to validate these findings.*
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  • The study describes a hereditary connective tissue disorder characterized by features like hyperextensible skin, joint laxity, and specific craniofacial characteristics linked to mutations in the EFEMP1 gene.
  • Genome sequencing revealed that both the proband and her mother carried a specific stop-gain mutation, leading to significantly reduced levels of the EFEMP1 transcript in their fibroblasts.
  • The findings highlight the role of EFEMP1 haploinsufficiency due to nonsense-mediated decay in causing severe symptoms, marking the first report of an autosomal dominant disorder associated with this gene and expanding the understanding of related conditions.
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Geleophysic dysplasia-1 (GD1) is an autosomal recessive disorder caused by ADAMTS-like 2 (ADAMTSL2) variants. It is characterized by distinctive facial features, limited joint mobility, short stature, brachydactyly, and life-threatening cardiorespiratory complications. The clinical spectrum spans from perinatal lethality to milder adult phenotypes.

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Background: We analyzed the genetic causes of sensorineural hearing loss in racial and ethnic minorities of South Florida by reviewing demographic, phenotypic, and genetic data on 136 patients presenting to the Hereditary Hearing Loss Clinic at the University of Miami. In our retrospective chart review, of these patients, half self-identified as Hispanic, and the self-identified racial distribution was 115 (86%) White, 15 (11%) Black, and 6 (4%) Asian. Our analysis helps to reduce the gap in understanding the prevalence, impact, and genetic factors related to hearing loss among diverse populations.

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Chanarin-Dorfman syndrome is an autosomal recessively inherited disorder characterized by ichthyosis, sensorineural hearing loss, and hepatic dysfunction. We report on a 60-year-old female of Venezuelan descent who presented with congenital ichthyosis, progressive sensorineural hearing loss, and liver cirrhosis. We identify a heterozygous copy number deletion involving exon 1 and another heterozygous deletion involving exon 3 of the ABHD5 gene.

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Hereditary hearing loss (HL) is a genetically heterogeneous disorder affecting people worldwide. The implementation of advanced sequencing technologies has significantly contributed to the identification of novel genes involved in HL. In this study, probands of two Turkish families with non-syndromic moderate HL were subjected to exome sequencing.

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Majority of 37 human aminoacyl tRNA synthetases have been incriminated in diverse, mostly recessive, genetic diseases. In accordance with this, we uncovered a novel homozygous valyl-tRNA synthetase 1 () gene variant, leading to p.T1068M mutation.

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Article Synopsis
  • Hearing loss (HL) is a common condition linked to over 200 different genes, prompting researchers to use exome and genome sequencing to find genetic causes in 322 families from Asia and Latin America.
  • The study found that variants in the GJB2 gene were present in 58 participants, but these were excluded from further analysis, as were 38 families with syndromic findings, leading to a focus on 212 families for further genetic testing.
  • Exome sequencing revealed 78 variants related to HL in 71 families, with a combined detection rate of 40% using both exome and genome sequencing, the latter proving effective in identifying difficult-to-detect variants in specific genetic regions.
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Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly, and facial dysmorphisms. A 4-year-old male with autism, developmental delay, microcephaly, and a happy demeanor underwent evaluation through the Undiagnosed Disease Network. He was clinically suspected to have Angelman syndrome; however, molecular testing was negative.

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Purpose: We compared next generation sequencing multigene panels (NGS-MGP) from 5 commercial laboratories to inform ophthalmologists' decision making in diagnostic genetic testing for congenital anterior segment anomalies (CASAs).

Design: Comparison of commercial genetic testing panels.

Methods: This observational study gathered publicly available information on NGS-MGP from 5 commercial laboratories for the following: cataracts, glaucoma, anterior segment dysgenesis (ASD), microphthalmia-anophthalmia-coloboma (MAC), corneal dystrophies, and Axenfeld-Rieger syndrome (ARS).

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Phenotypic features of KBG syndrome include craniofacial anomalies, short stature, cognitive disability and behavioral findings. The syndrome is caused by heterozygous pathogenic single nucleotide variants and indels in ANKRD11, or a heterozygous deletion of 16q24.3 that includes ANKRD11.

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Background: Early-onset glaucoma is a potentially sight-threatening condition with high heritability. Next generation sequencing is a cost-effective alternative to individual gene screening that could expedite its diagnosis. However, the diagnostic yield of multigene panel assays for early-onset glaucoma varies according to the tested population.

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  • Discovery of deafness genes has enhanced our understanding of hearing mechanisms and associated disorders, with findings from four families linking mutations in the NOTCH2-associated receptor (MINAR2) to autosomal recessive nonsyndromic deafness.
  • Three specific genetic variants related to severe-to-profound hearing loss were identified, and one variant was found to disrupt normal splicing of RNA.
  • Research shows that MINAR2 is critical for hearing, with its absence in mice leading to severe hearing loss and hair cell damage, suggesting potential for genetic therapies to mitigate hearing loss progression.
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Neurodegenerative disorders and leukodystrophies are progressive neurologic conditions that can occur following the disruption of intricately coordinated patterns of gene expression. Exome sequencing has been adopted as an effective diagnostic tool for determining the underlying genetic etiology of Mendelian neurologic disorders, however genome sequencing offer advantages in its ability to identify and characterize copy number, structural, and sequence variants in noncoding regions. Genome sequencing from peripheral leukocytes was performed on two patients with progressive neurologic disease of unknown etiology following negative genetic investigations including exome sequencing.

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Hearing loss (HL) is one of the most common sensory defects, of which X-linked nonsyndromic hearing loss (NSHL) accounts for only 1-2%. While a COL4A6 variant has been reported in a single Hungarian family with NSHL associated with inner ear malformation, causative role of COL4A6 variants and their phenotypic consequences in NSHL remain elusive. Here we report two families in which we identified a male member with X-linked HL.

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Peroxisomes play an essential role in lipid metabolism via interaction with other intracellular organelles. The information about the role of the Acyl-CoA-binding domain containing-protein 5 (ACBD5) in these interactions in human cells is emerging. Moreover, a few patients with retinal dystrophy and leukodystrophy caused by pathogenic variants in ACBD5 have been recently introduced.

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The stereocilia of the inner ear sensory cells contain the actin-binding protein radixin, encoded by RDX. Radixin is important for hearing but remains functionally obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to visualize stereocilia motion while measuring electrical potential amplitudes during acoustic stimulation.

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Galactosemia is a rare, treatable hereditary disorder of carbohydrate metabolism. We investigated the etiology of decreased GALT enzyme activity in a cohort of newborns referred by the Florida Newborn Screening Program with no detectable GALT variants in diagnostic molecular tests. Six affected individuals from four families with Guatemalan heritage were included.

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Molecular mechanisms governing the development of the mammalian cochlea, the 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 in a noncoding region on chromosome 8 with an approximately 200-kb overlapping section. Genomic location of the overlapping deleted region started from approximately 350 kb downstream of GDF6, which codes for growth and differentiation factor 6.

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Anterior segment dysgenesis (ASD) comprises a wide spectrum of developmental conditions affecting the cornea, iris, and lens, which may be associated with abnormalities of other organs. To identify disease-causing variants, we performed exome sequencing in 24 South Florida families with ASD. We identified 12 likely causative variants in 10 families (42%), including single nucleotide or small insertion-deletion variants in B3GLCT, BMP4, CYP1B1, FOXC1, FOXE3, GJA1, PXDN, and TP63, and a large copy number variant involving PAX6.

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