Publications by authors named "Asli Subasioglu"

11 Publications

  • Page 1 of 1

Radixin modulates the function of outer hair cell stereocilia.

Commun Biol 2020 Dec 23;3(1):792. Epub 2020 Dec 23.

Department of Biomedical and Clinical Sciences, Linköping University, SE-581 83, Linköping, Sweden.

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. Radixin inhibition decreased sound-evoked electrical potentials. Other functional measures, including electrically induced sensory cell motility and sound-evoked stereocilia deflections, showed a minor amplitude increase. These unique functional alterations demonstrate radixin as necessary for conversion of sound into electrical signals at acoustic rates. We identified patients with RDX variants with normal hearing at birth who showed rapidly deteriorating hearing during the first months of life. This may be overlooked by newborn hearing screening and explained by multiple disturbances in postnatal sensory cells. We conclude radixin is necessary for ensuring normal conversion of sound to electrical signals in the inner ear.
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http://dx.doi.org/10.1038/s42003-020-01506-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758333PMC
December 2020

Treatment of three hereditary leiomyomatosis patients with cryotherapy.

Dermatol Ther 2020 03 19;33(2):e13226. Epub 2020 Jan 19.

Department of Medical Genetics, Ataturk Training and Research Hospital, Izmir Katip Celebi University, Izmir, Turkey.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is an autosomal dominant disorder characterized by cutaneous leiomyomas (CLM), uterine leiomyomas, and the increased risk of renal cell carcinoma. Piloleiomyomas develop from the arrectorpili muscle and are usually painful. For 22% of the affected patients, the pain is reported to impair their life quality. Since there are few case reports about cryotherapy for cutaneous leiomyomas in the literature, we have decided to present three patients who had painful cutaneous leiomyomas treated with cryotherapy.
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http://dx.doi.org/10.1111/dth.13226DOI Listing
March 2020

Dysfunction of , encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss.

Proc Natl Acad Sci U S A 2019 01 4;116(4):1347-1352. Epub 2019 Jan 4.

John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136;

We have identified a variant (c.311A>T; p.Gln104Leu) cosegregating with autosomal recessive nonsyndromic deafness in two unrelated families. encodes a member of the highly conserved growth factor receptor-bound protein 2 (GRB2)/Sem-5/drk family of proteins, which are involved in Ras signaling; however, the function of the growth factor receptor-bound protein 2 (GRB2)-related adaptor protein (GRAP) in the auditory system is not known. Here, we show that, in mouse, is expressed in the inner ear and the protein localizes to the neuronal fibers innervating cochlear and utricular auditory hair cells. Downstream of receptor kinase (), the homolog of human , is expressed in Johnston's organ (JO), the fly hearing organ, and the loss of in JO causes scolopidium abnormalities. mutant flies present deficits in negative geotaxis behavior, which can be suppressed by human wild-type but not mutant GRAP. Furthermore, drk specifically colocalizes with synapsin at synapses, suggesting a potential role of such adaptor proteins in regulating actin cytoskeleton dynamics in the nervous system. Our findings establish a causative link between mutation and nonsyndromic deafness and suggest a function of GRAP/drk in hearing.
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http://dx.doi.org/10.1073/pnas.1810951116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347722PMC
January 2019

Research of genetic bases of hereditary non-syndromic hearing loss.

Turk Pediatri Ars 2017 Sep 1;52(3):122-132. Epub 2017 Sep 1.

Department of Medical Genetics, Erciyes University Faculty of Medicine, Kayseri, Turkey.

Aim: Hearing loss is the most common sensory disorder that affects approximately one per 1000 live births. With this project, we aimed to identify gene variants that were common causes of hearing loss in Turkey to contribute to the planning of genetic screening programs for hearing loss, as well as to improve genetic counseling to affected families.

Material And Methods: Twenty-one families with at least two affected individuals and parental consanguinity who presented with non-syndromic severe-to-profound sensorineural hearing loss were included in this study. We first screened for mutations in GJB2 and mitochondrial DNA 12S RNA genes. Subsequently, we genotyped the TMIE c.250C>T and SNP markers flanking the genes in the remaining twelve families without mutations in GJB2.

Results: Screening for mutations in GJB2 gene showed c.[35delG];[35delG] mutation in four families, c.[35delG];[507C>A] mutation in two families, c.[35delG];[-23+1G>A] mutation in one family, and c.457G>A heterozygous mutation in one family. Genotyping SNP markers showed the c.[250C>T];[250C>T] mutation in TMIE in one family. A homozygous region with SNP genotypes was detected with the gene in one family, the gene in another family, and also a homozygous region was detected with , and genes in another family.

Conclusions: Further research will be required to determine the genetic bases of hearing loss in families with non-syndromic hearing loss.
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http://dx.doi.org/10.5152/TurkPediatriArs.2017.4254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644578PMC
September 2017

The effect of the additional cytogenetic abnormalities on major molecular response and BCR-ABL kinase domain mutations in long-term follow-up chronic myeloid leukemia patients, a cross sectional study.

Leuk Lymphoma 2017 08 7;58(8):1958-1962. Epub 2016 Dec 7.

b Department of Hematology , Izmir Ataturk Education and Research Hospital , Izmir , Turkey.

The aim of the study was to examine the relation between additional chromosomal aberrations (ACAs) with major molecular response (MMR) and BCR-ABL kinase domain (KD) mutations in the long-term follow-up of the chronic myeloid leukemia (CML) disease. The study design was cross-sectional observational and used the CML patients' data of Izmir Ataturk Education and Research Hospital from 2011 to 2015. Conventional cytogenetic, fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (RQ-PCR) test results from 89 CML patients' and pyrosequencing analysis results from 17 patients' were set up for comparison analysis. The chi-square test was used in statistical analysis of the experimental data. There were no statistically significant correlations between ACAs and MMR (p = .361, p > .05) groups or BCR-ABL KD mutations (p = .576, p > .05) groups observed in the study. This study has revealed that MMR and BCR-ABL KD mutations did not correlate with ACAs.
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http://dx.doi.org/10.1080/10428194.2016.1265112DOI Listing
August 2017

The effect of parental 5,10-methylenetetrahydrofolate reductase 677C/T and 1298A/C gene polymorphisms on response to single-dose methotrexate in tubal ectopic pregnancy.

J Matern Fetal Neonatal Med 2017 May 2;30(10):1232-1237. Epub 2016 Aug 2.

b Department of Medical Genetics , Faculty of Medicine, Erciyes University , Kayseri , Turkey.

Object: The aim of this study was to assess the effect of parental 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C/T and 1298A/C) on response to single-dose methotrexate (MTX) treatment in tubal ectopic pregnancy (TEP).

Materials And Methods: In this prospective cohort study, cases with unruptured TEPs were grouped into two according to their response to single-dose MTX treatment (Group 1: responsive, n:88; Group 2: unresponsive, n:21). The groups were compared with regard to baseline demographic and clinical parameters. As a main outcome measure, the independent effects of parental MTHFR gene polymorphisms on response to single dose MTX treatment were evaluated.

Results: One hundred and nine unruptured TEP were included in the final analysis. The mean maternal age was 29.30 ± 5.21 years, gravity 2 (min-max: 1-5), parity 1 (min-max: 0-4). The median serum beta-human chorionic gonadotropin (β-hCG) was 1403.35 MI/I (Q-Q: 517-2564). The overall response rate was 81% (88/109). The groups were similar with respect to basic baseline demographic data and serum β-hCG level. Binary logistic regression analysis showed that the presence of parental MTHFR677C/T and 1298A/C polymorphism were not independent factor predicting treatment success (p > 0.05). The only independent factor for resistance to single dose MTX was the previous TEP (OR: 4.47 (1.18-16.9)).

Conclusion: Parental MTHFR 677C/T and 1298A/C mutations do not predict the outcome of single dose intramuscular MTX treatment in unruptured TEP.
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http://dx.doi.org/10.1080/14767058.2016.1209652DOI Listing
May 2017

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort.

Genet Med 2016 Apr 30;18(4):364-71. Epub 2015 Jul 30.

Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

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.Genet Med 18 4, 364-371.
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http://dx.doi.org/10.1038/gim.2015.89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733433PMC
April 2016

Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.

BMC Med Genet 2015 Feb 25;16. Epub 2015 Feb 25.

John P. Hussmann Institute for Human Genomics and John T. Macdonald Foundation, Department of Human Genetics, Miller school of Medicine, University of Miami, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA.

Background: Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies.

Methods: Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families.

Results: Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families.

Conclusions: Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.
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http://dx.doi.org/10.1186/s12881-015-0149-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422282PMC
February 2015

A Glutamine Repeat Variant of the RUNX2 Gene Causes Cleidocranial Dysplasia.

Mol Syndromol 2015 Feb 29;6(1):50-3. Epub 2015 Jan 29.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Cleidocranial dysplasia (CCD), an autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles and delayed closure of the cranial sutures, is caused by mutations of the runt-related transcription factor 2 (RUNX2) gene. The RUNX2 gene consists of a glutamine and alanine repeat domain (Q/A domain, 23Q/17A), a DNA-binding Runt domain and a proline/serine/threonine-rich domain. We report on a familial case of CCD with a novel mutation within the Q/A domain of the RUNX2 gene, which is an insertion in exon 1 (p.Q71_E72insQQQQ) representing the Q-repeat variant (27Q/17A). Functional analysis of the 27Q variant revealed abolished transactivation capacity of the mutated RUNX2 protein. This is the first case report that demonstrated a glutamine repeat variant of the RUNX2 gene causes CCD.
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http://dx.doi.org/10.1159/000370337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369121PMC
February 2015

Emopamil binding protein mutation in conradi-hünermann-happle syndrome representing plaque-type psoriasis.

Indian J Dermatol 2015 Mar-Apr;60(2):216

Department of Molecular Medicine, University of Salamanca, Salamanca, Spain.

Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones, and eyes. CDPX2 patients display skin defects, including ichthyotic lesions, follicular atrophoderma, cicatricial alopecia, and less frequently ichthyosiform erythroderma, cataracts, and skeletal abnormalities consisting of short stature, asymmetric shortening of the limbs, epiphyseal stippling, and craniofacial defects. CDPX2 results from mutations in emopamil binding protein (EBP) gene. The aim of our study is to identify EBP mutation in a unique case of Conradi-Hünermann-Happle syndrome with rare psoriasiform lesions.
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http://dx.doi.org/10.4103/0019-5154.152570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372958PMC
March 2015

Genetic background of supernumerary teeth.

Eur J Dent 2015 Jan-Mar;9(1):153-158

Department of Medical Genetics, Medical Faculty, Erciyes University, Kayseri, Turkiye.

Supernumerary teeth (ST) are odontostomatologic anomaly characterized by as the existence excessive number of teeth in relation to the normal dental formula. This condition is commonly seen with several congenital genetic disorders such as Gardner's syndrome, cleidocranial dysostosis and cleft lip and palate. Less common syndromes that are associated with ST are; Fabry Disease, Ellis-van Creveld syndrome, Nance-Horan syndrome, Rubinstein-Taybi Syndrome and Trico-Rhino-Phalangeal syndrome. ST can be an important component of a distinctive disorder and an important clue for early diagnosis. Certainly early detecting the abnormalities gives us to make correct management of the patient and also it is important for making well-informed decisions about long-term medical care and treatment. In this review, the genetic syndromes that are related with ST were discussed.
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http://dx.doi.org/10.4103/1305-7456.149670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319293PMC
February 2015