Yazar "Duman, Duygu" seçeneğine göre listele

Listeleniyor 1 - 6 / 6
  • [ 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
    Genome sequencing identifies coding and non-coding variants for non-syndromic hearing loss
    (Springernature, 2023) Ramzan, Memoona; Duman, Duygu; Hendricks, LeShon Chere Peart; Guo, Shengru; Mutlu, Ahmet; Kalcioglu, Mahmut Tayyar; Seyhan, Serhat
    Hearing loss (HL) is a common heterogeneous trait that involves variants in more than 200 genes. In this study, we utilized exome (ES) and genome sequencing (GS) to effectively identify the genetic cause of presumably non-syndromic HL in 322 families from South and West Asia and Latin America. Biallelic GJB2 variants were identified in 58 probands at the time of enrollment these probands were excluded. In addition, upon review of phenotypic findings, 38/322 probands were excluded based on syndromic findings at the time of ascertainment and no further evaluation was performed on those samples. We performed ES as a primary diagnostic tool on one or two affected individuals from 212/226 families. Via ES we detected a total of 78 variants in 30 genes and showed their co-segregation with HL in 71 affected families. Most of the variants were frameshift or missense and affected individuals were either homozygous or compound heterozygous in their respective families. We employed GS as a primary test on a subset of 14 families and a secondary tool on 22 families which were unsolved by ES. Although the cumulative detection rate of causal variants by ES and GS is 40% (89/226), GS alone has led to a molecular diagnosis in 7 of 14 families as the primary tool and 5 of 22 families as the secondary test. GS successfully identified variants present in deep intronic or complex regions not detectable by ES.
  • [ X ]
    Öğe
    MASP1 Mutations in Patients with Facial, Umbilical, Coccygeal, and Auditory Findings of Carnevale, Malpuech, OSA, and Michels Syndromes
    (Cell Press, 2010) Sirmaci, Asli; Walsh, Tom; Akay, Hatice; Spiliopoulos, Michail; Sakalar, Yildirim Bayezit; Hasanefendioglu-Bayrak, Aylin; Duman, Duygu
    Distinctive facial features consisting of hypertelorism, telecanthus, blepharophimosis blepharoptosis, epicanthus inversus, periumbil seal defects, and skeletal anomalies are seen in autosomal recessive Carnevale, Malpuech, Michels, and oculo skeletal abdominal (OSA) syndromes The gene or genes responsible for these syndromes were heretofore unknown We report on three individuals from two consanguineous Turkish families with findings characteristic of these syndromes including facial dysmorphism periumbilical depression mixed hearing loss, radioulnar synostosis and coccygeal appendage Homozygosity mapping yielded an autozygous region on chromosome 3q27 in both families In one family, whole exome sequencing revealed a missense mutation, MASP1 c 2059G>A (p G687R) that cosegregated with the phenotype In the second family, Sanger sequencing of MASP1 revealed a nonsense mutation, MASP1 c 870G>A (p W290X) that also cosegregated with the phenotype Neither mutation was found in 192 Turkish controls or 1200 controls of various other ancestries MASP1 encodes mannan binding lectin senne protease 1 The two mutations occur in a MASP1 isoform that has been reported to process IGFBP 5 thereby playing a critical role in insulin growth factor availability during craniofacial and muscle development These results implicate mutations of MASP1 as the cause of a human malformation syndrome and demonstrate the involvement of MASP1 in facial, umbilical, and ear development during the embryonic period
  • [ X ]
    Öğe
    Mutations in TMC1 contribute significantly to nonsyndromic autosomal recessive sensorineural hearing loss: A report of five novel mutations
    (Elsevier Ireland Ltd, 2009) Sirmaci, Asli; Duman, Duygu; Ozturkmen-Akay, Hatice; Erbek, Seyra; Incesulu, Armagan; Ozturk-Hismi, Burcu; Arici, Z. Serap
    Genome wide homozygosity mapping using Affymetrix 10K arrays revealed the DFNB7/11 locus including the TMC1 gene in 5 of 35 Turkish families with autosomal recessive nonsyndromic severe to profound congenital or prelingual-onset sensorineural hearing loss (SNHL). Additional 51 families were later screened for co-segregation of the locus with the phenotype using microsatellite markers. GJB2 and mtDNA A1555G mutations were negative in probands from each family. Mutation analysis was performed in families showing co-segregation Of autosomal recessive SNHL with haplotypes at the DFNB7/11 locus. A total of six different mutations in seven families were identified, including novel missense alterations, p.G444R (c.1330G > A), p.R445C (c.1333C > T), and p.1677T (c.2030T > C), one novel splice site mutation IVS6+2 T > A (c.64+2T > A), and a novel large deletion ofapproximately 31 kb at the 3' region of the gene including exons 19-24, as well as a previously reported nonsense mutation, p.R34X (c.100C > T). All identified Mutations co-segregated with autosomal recessive SNHL in all families and were not found in Turkish hearing controls. These results expand the mutation spectrum of TMC1 with five novel mutations and provide data for the significant contribution of TMC1 mutations in hearing loss. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
  • [ X ]
    Öğe
    A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss
    (Springer, 2019) Sineni, Claire J.; Yildirim-Baylan, Muzeyyen; Guo, Shengru; Camarena, Vladimir; Wang, Gaofeng; Tokgoz-Yilmaz, Suna; Duman, Duygu
    While the importance of tight junctions in hearing is well established, the role of Claudin- 9 (CLDN9), a tight junction protein, in human hearing and deafness has not been explored. Through whole-genome sequencing, we identified a one base pair deletion (c.86delT) in CLDN9 in a consanguineous family from Turkey with autosomal recessive nonsyndromic hearing loss. Three affected members of the family had sensorineural hearing loss (SNHL) ranging from moderate to profound in severity. The variant is predicted to cause a frameshift and produce a truncated protein (p.Leu29ArgfsTer4) in this single-exon gene. It is absent in public databases as well as in over 1000 Turkish individuals, and co-segregates with SNHL in the family. Our in vitro studies demonstrate that the mutant protein does not localize to cell membrane as demonstrated for the wild-type protein. Mice-lacking Cldn9 have been shown to develop SNHL. We conclude that CLDN9 is essential for proper audition in humans and its disruption leads to SNHL in humans.