Yazar "Bademci, Guney" seçeneğine göre listele

Listeleniyor 1 - 3 / 3
  • [ X ]
    Öğe
    Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort
    (Nature Publishing Group, 2016) Bademci, Guney; Foster, Joseph, II; Mahdieh, Nejat; Bonyadi, Mortaza; Duman, Duygu; Cengiz, F. Basak; Menendez, Ibis
    Purpose: Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES). Methods: After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes. Results: We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared-haplotypes, suggesting founder effects. Conclusion: We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining-families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.
  • [ X ]
    Öğe
    Evidence for genotype-phenotype correlation for OTOF mutations
    (Elsevier Ireland Ltd, 2014) Yildirim-Baylan, Muzeyyen; Bademci, Guney; Duman, Duygu; Ozturkmen-Akay, Hatice; Tokgoz-Yilmaz, Suna; Tekin, Mustafa
    Objectives: The aim of this study is to evaluate the auditory phenotype in subjects with OTOF gene mutations to describe genotype-phenotype correlations. Methods: Twenty-two affected members from three families with homozygous OTOF mutations were included. Nine subjects were evaluated audiologically with otoscopic examination, pure-tone audiometry, tympanometry with acoustic reflex testing, auditory brain stem responses, and otoacoustic emission tests. Results: Homozygous c.4718T>C (p.Ile1573Thr) mutation was associated with the auditory neuropathy/auditory dys-synchrony (AN/AD) phenotype and with progressive sensorineural hearing loss in four siblings in one family, while homozygous c.4467dupC (p.I1490HfsX19) was associated with severe to profound sensorineural hearing loss without AN/AD in four relatives in another family. Homozygous c.1958delC (p.Pro653LeufsX13) mutation was associated with moderate sensorineural hearing loss without AN/AD in one affected person in an additional family. Conclusions: The audiological phenotype associated with different OTOF mutations appears to be consistently different suggesting the presence of a genotype-phenotype correlation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
  • [ X ]
    Öğe
    Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
    (Natl Acad Sciences, 2022) Bademci, Guney; Lachgar-Ruiz, Maria; Deokar, Mangesh; Zafeer, Mohammad Faraz; Abad, Clemer; Baylan, Muzeyyen Yildirim; Ingham, Neil J.
    Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding of hearing physiology and its pathologies. Here we report on DNA variants in MINAR2, encoding membrane integral NOTCH2-associated receptor 2, in four families underlying autosomal recessive nonsyndromic deafness. Neurologic evaluation of affected individuals at ages ranging from 4 to 80 y old does not show additional abnormalities. MINAR2 is a recently annotated gene with limited functional understanding. We detected three MINAR2 variants, c.144G > A (p.Trp48*), c.412_419de1CGGTTTTG (p.Arg138Valfs*10), and c.393G > T, in 13 individuals with congenital- or prelingual-onset severe-to-profound sensorineural hearing loss (HL). The c.393G > T variant is shown to disrupt a splice donor site. We show that Minar2 is expressed in the mouse inner ear, with the protein localizing mainly in the hair cells, spiral ganglia, the spiral limbus, and the stria vascularis. Mice with loss of function of the Minar2 protein (Minar2(tm1b/tm1b)) present with rapidly progressive sensorineural HL associated with a reduction in outer hair cell stereocilia in the shortest row and degeneration of hair cells at a later age. We conclude that MINAR2 is essential for hearing in humans and mice and its disruption leads to sensorineural HL. Progressive HL observed in mice and in some affected individuals and as well as relative preservation of hair cells provides an opportunity to interfere with HL using genetic therapies.