Yazar "Yalcintepe, Sinem" seçeneğine göre listele

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    The Application of Next Generation Sequencing Maturity Onset Diabetes of the Young Gene Panel in Turkish Patients from Trakya Region
    (Galenos Yayincilik, 2021) Yalcintepe, Sinem; Comlek, Fatma Ozguc; Gurkan, Hakan; Demir, Selma; Atli, Emine Ikbal; Atli, Engin; Eker, Damla
    Objective: The aim of this study was to investigate the molecular basis of maturity-onset diabetes of the young (MODY) by targeted-gene sequencing of 20 genes related to monogenic diabetes, estimate the frequency and describe the clinical characteristics of monogenic diabetes and MODY in the Trakya Region of Turkey. Methods: A panel of 20 monogenic diabetes related genes were screened in 61 cases. Illumina NextSeq550 system was used for sequencing. Pathogenicity of the variants were assessed by bioinformatics prediction software programs and segregation analyses. Results: In 29 (47.5%) cases, 31 pathogenic/likely pathogenic variants in the GCK, ABCC8, KCNJ11, HNF1A, HNF4A genes and in 11 (18%) cases, 14 variants of uncertain significance (VUS) in the GCK, RFX6, CEL, PDX1, KCNJ11, HNF1A, G6PC2, GLIS3 and KLF11 genes were identified. There were six different pathogenic/likely pathogenic variants and six different VUS which were novel. Conclusion: This is the first study including molecular studies of twenty monogenic diabetes genes in Turkish cases in the Trakya Region. The results showed that pathogenic variants in the GCK gene are the leading cause of MODY in our population. A high frequency of novel variants (32.4%-12/37) in the current study, suggests that multiple gene analysis provides accurate genetic diagnosis in MODY.
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    A Child with 5q Deletion and Accompanying Chiari 1 Malformation
    (Springer India, 2020) Atli, Emine Ikbal; Yalcintepe, Sinem; Atli, Engin; Demir, Selma; Gurkan, Hakan
    [Abstract Not Available]
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    Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders
    (Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2020) Gurkan, Hakan; Atli, Emine Ikbal; Atli, Engin; Bozatli, Leyla; Altay, Menguhan Araz; Yalcintepe, Sinem; Ozen, Yasemin
    Introduction: Aneuploids, copy number variations (CNVs), and single nucleotide variants in specific genes are the main genetic causes of developmental delay (DD) and intellectual disability disorder (IDD). These genetic changes can be detected using chromosome analysis, chromosomal microarray (CMA), and next-generation DNA sequencing techniques. Therefore; In this study, we aimed to investigate the importance of CMA in determining the genomic etiology of unexplained DD and IDD in 123 patients. Method: For 123 patients, chromosome analysis, DNA fragment analysis and microarray were performed. Conventional G-band karyotype analysis from peripheral blood was performed as part of the initial screening tests. FMR1 gene CGG repeat number and methylation analysis were carried out to exclude fragile X syndrome. Results: CMA analysis was performed in 123 unexplained IDD/DD patients with normal karyotypes and fragile X screening, which were evaluated by conventional cytogenetics. Forty-four CNVs were detected in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients were reported. In 6 patients, one or more pathogenic CNVs were determined. Therefore, the diagnostic efficiency of CMA was found to be 31.7% (39/123). Conclusion: Today, genetic analysis is still not part of the routine in the evaluation of IDD patients who present to psychiatry clinics. A genetic diagnosis from CMA can eliminate genetic question marks and thus alter the clinical management of patients. Approximately one-third of the positive CMA findings are clinically intervenable. However, the emergence of CNVs as important risk factors for multiple disorders increases the need for individuals with comorbid neurodevelopmental conditions to be the priority where the CMA test is recommended.
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    Clinical exome sequencing reveals an important role for clinical diagnosis of intellectual disability with definition of seven novel variants
    (Asean Neurological Assoc, 2023) Yalcintepe, Sinem; Gorker, Isik; Bozatli, Leyla; Guler, Hazal Sezginer; Zhuri, Drenushe; Demir, Selma; Atli, Emine Ikbal
    Intellectual disability can be defined as a significantly below-average general mental function, accompanied by environmental adaptation and behavioural deterioration. Patient files of 87 children with intellectual disability were evaluated in this study. After clinical exclusion criterias, clinical exome sequencing was performed for 25 of 87 intellectual disability cases with a massively parallel targeted sequencing method. Seventeen variants in the genes MBOAT7, KDM5C, TUBB3, MAN1B1, GFAP, CACNA1A, BCOR, LMNA, LBR, ALS2, ENPP1, UBE3A, TRAPPC9, HSPG2, AFF2, NLGN4, and SOX10 were identified in 14 of 25 patients (56%). Seven of the 17 variants (41.1%) were novel in the genes KDM5C, BCOR, UBE3A, TRAPPC9, AFF2, NLGN4, and SOX10. Seven cases (7/25, 28%) had a definite diagnosis of intellectual disability with their pathogenic variants. The high rate of variant detection (56%) in the current study shows that multiple gene analysis plays an essential role in diagnosing the uncertain etiology of intellectual disability. This study also presents seven novel variants, which are first reported.
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    Clinical Implications of Chromosome 16 Copy Number Variation
    (Karger, 2022) Atli, Emine Ikbal; Yalcintepe, Sinem; Atli, Engin; Demir, Selma; Mail, Cisem; Gurkan, Hakan
    Chromosome 16 is one of the gene-rich chromosomes; however, approximately 10% of the chromosome 16 sequence is composed of segmental copies, which renders this chromosome instable and predisposes it to rearrangements via frequent nonallelic homologous recombination. Microarray technologies have enabled the analysis of copy number variations (CNV), which may be associated with the risk of developing complex diseases. Through comparative genomic hybridisation in 1,298 patients, we detected 18 cases with chromosome 16 CNV. We identified 2recurrent CNV regions, including 1 at 16p13.11 in 4 patients and another at 16p11.2 in 7 patients. We also detected atypical chromosome 16 rearrangements in 7 patients. Furthermore, we noted an increased frequency of co-occurring genomic changes, supporting the two-hit hypothesis to explain the phenotypic variability in the clinical presentation of CNV syndromes. Our findings can contribute to the creation of a chromosome 16 disease map based on regions that may be associated with disease development.
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    Comprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic KRAS Variation
    (Karger, 2022) Demir, Selma; Kostek, Huemeyra Yasar; Sanri, Aslihan; Yildirim, Ruken; Comlek, Fatma Oezguec; Yalcintepe, Sinem; Deveci, Murat
    Introduction: Germline pathogenic variations of the genes encoding the components of the Ras-MAPK pathway are found to be responsible for RASopathies, a clinically and genetically heterogeneous group of diseases. In this study, we aimed to present the results of patients genetically investigated for RASopathy-related mutations in our Genetic Diagnosis Center. Methods: The results of 51 unrelated probands with RASopathy and 4 affected relatives (31 male, 24 female; mean age: 9.327 +/- 8.214) were included in this study. Mutation screening was performed on DNA samples from peripheral blood of the patients either by Sanger sequencing of PTPN11 hotspot regions (10/51 probands), or by a targeted amplicon next-generation sequencing panel (41/51 probands) covering the exonic regions of BRAF, CBL, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, RASA2, RIT1, SHOC2, SOS1, SOS2, SPRED1, and KAT6B genes. Results: Pathogenic/likely pathogenic variations found in 22 out of 51 probands (43.13%) and their 4 affected family members were located in PTPN11, BRAF, KRAS, NF1, RAF1, SOS1, and SHOC2 genes. The c.148A>C (p.Thr50Pro) variation in the KRAS gene was a novel variant detected in a sibling in our patient cohort. We found supportive evidence for the pathogenicity of the NF1 gene c.5606G>T (p.Gly1869Val) variation which we defined in an affected boy who inherited the mutation from his affected father. Conclusion: Although PTPN11 is the most frequently mutated gene in our patient cohort, as in most previous reports, different mutation distribution among the other genes studied motivates the use of a next-generation sequencing gene panel including the possible responsible genes.
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    Comprehensive Genetic Analysis Results of TSC1/TSC2 Genes in Patients with Clinical Suspicion of Tuberous Sclerosis Complex and Definition of 3 Novel Variants
    (Galenos Publ House, 2021) Demir, Selma; Yalcintepe, Sinem; Atli, Engin; Yalcin, Yelda; Atli, Emine Ikbal; Eker, Damla; Karal, Yasemin
    Background: Tuberous Sclerosis Complex is an autosomal dominant multi-system disorder with an incidence of about 1 in 6000 live births. Defects in either TSC1 (* 605284) or TSC2 (* 191092) genes encoding the components of the Tuberous Sclerosis Complex are responsible for the disease. Therefore, consideration of TSC1/TSC2 pathogenic variations is recommended in the updated diagnostic criteria of Tuberous Sclerosis Complex. Aims: To present the TSC1/TSC2 screening results of a mixed patient population as well as possible new variants in 23 cases from 20 different families who were referred to our Genetic Diseases Diagnosis Center with the signs and symptoms of Tuberous Sclerosis Complex. Study design: Retrospective, cross-sectional study. Methods: Germline TSC1/TSC2 variants were screened in DNA samples extracted from peripheral blood samples of 23 patients from 20 unrelated families using targeted high-throughput sequencing and multiplex ligation-dependent probe amplification methods. The variants identified were classified according to ACMG 2015 guidelines. Results: In total, 5 different pathogenic/likely pathogenic changes have been defined. All these pathogenic/likely pathogenic variants were located in the TSC2 gene. Three of the pathogenic/likely pathogenic variants were novel. Two patients who are twin sisters were found to have TSC2/PKD1 contiguous deletion syndrome. One of the 3 novel variants was a mosaic in-frame deletion. We did not identify any pathogenic variants of the TSC1 gene. Conclusion: The novelty of most of the variants found, including a mosaic likely pathogenic variant, and the presence of a large genomic rearrangement, supports the importance of a comprehensive approach in analyzing TSC1/TSC2 genes. Genetic diagnosis should be performed with caution, considering the possibility of mosaic variants with low allelic fractions.
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    The Correlation of Cystic Fibrosis Screening Test Results with Ultrasonographically Detected Fetal Anomalies in Prenatal Diagnosis
    (Galenos Publ House, 2023) Atli, Emine Ikbal; Atli, Engin; Demir, Selma; Yalcintepe, Sinem; Gurkan, Hakan
    Objective: In a multiethnic community, our goal was to assess the applicability of this method. Here we offer a collection of 112 diagnostic prenatal samples for which a comprehensive study of exons, exons/intron boundaries, and major rearrangements has been investigated in prenatal samples of fetuses with suspected cystic fibrosis over the past decade.Methods: For the CFTR mutation study, 112 prenatal samples (amniotic fluid, chorionic villi, or cultured cells from amniotic fluid or chorionic villi) were brought into our lab. QIAseq Targeted NGS DNA Panel (Qiagen, Hilden, Germany) was performed to analyze the CFTR gene (27 exons).Results: The pathogenic variation NM000492.4(CFTR):c.3454G>C was the most often found (p.Asp1152His), which accounted for 50% of the classic pathogenic CF variants in the study population. Compound heterozygous CFTR pathogenic variations were detected in one of our patients. NM000492.3(CFTR):c.2620-15C>G and NM000492.3(CFTR):c.2756A>G Two variants, one of which was reported as VUS and the other as pathogenic, were detected in a 17-week -old fetus (0.89%). Fetus inherited the NM000492.3(CFTR):c.2756A>G variant from mother and the NM000492.3(CFTR):c.2620-15C>G variant from father. There is an isolated hyperechoic bowel sign at 17 weeks of pregnancy.Conclusion: In our case series, genetic analyzes suggest that an affected child may be heterozygous for CFTR mutations, compound heterozygous for two clinically significant recessive mutations inherited from healthy carrier parents. Early prenatal genetic testing pretesting and posttesting genetic counseling is crucial in the management of future pregnancies in heterozygous couples which are healthy carriers for CFTR mutations.
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    Customised targeted massively parallel sequencing enables more precisely diagnosis of patients with epilepsy
    (Wiley, 2022) Atli, Emine Ikbal; Atli, Engin; Yalcintepe, Sinem; Demir, Selma; Kalkan, Rasime; Eker, Damla; Gurkan, Hakan
    Background Advancement in genetic technology has led to the identification of an increasing number of genes in epilepsy. This will provide a lot of information in clinical practice and improve the diagnosis and treatment of epilepsy. Aim To show the importance of genes in the next-generation sequencing (NGS) panel during the evaluation of epilepsy and to emphasise the importance of genetic studies in different populations for the evaluation of genes that cause disease. Methods This was a single-centre retrospective cohort study of 80 patients who underwent NGS testing with a customised epilepsy panel. Results In a total of 54 (67.5%) out of 80 patients, pathogenic or likely pathogenic variants and variants of uncertain significance (VOUS) were identified according to the American College of Medical Genetics and Genomics criteria. Pathogenic or likely pathogenic variants (n = 35) were identified in 29 (36.25%) out of 80 individuals. VOUS (n = 34) were identified in 28 (35%) out of 80 patients. Pathogenic, likely pathogenic and VOUS were most frequently identified in TSC2 (n = 11), SCN1A (n = 6) and TSC1 (n = 5) genes. Other common genes were KCNQ2 (n = 3), AMT (n = 3), CACNA1H (n = 3), CLCN2 (n = 3), MECP2 (n = 2), ASAH1 (n = 2) and SLC2A1 (n = 2). Conclusions NGS-based testing panels contribute to the diagnosis of epilepsy and might change the clinical management by preventing unnecessary and potentially harmful diagnostic procedures and management in patients. Thus, our results highlight the benefit of genetic testing in children suffering with epilepsy.
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    Diagnostic Value of Microarray Method in Autism Spectrum Disorder, Intellectual Disability, and Multiple Congenital Anomalies and Some Candidate Genes for Autism: Experience of Two Centers
    (Galenos Publ House, 2022) Ayaz, Akif; Gezdirici, Alper; Gulec, Elif Yilmaz; Ozalp, Ozge; Koseoglu, Abdullah Huseyin; Dogru, Zeynep; Yalcintepe, Sinem
    Objective: This study aimed to demonstrate the diagnostic value of microarray testing in autism spectrum disorder, intellectual disability, and multiple congenital anomalies of unknown etiology, as well as to report some potential candidate genes for autism. Methods: Microarray analysis records between January 2016 and December 2017 from two Genetic Diagnostic Centers in Turkey, Kanuni Sultan Suleyman and Adana Numune Training and Research Hospital, were compiled. Detected copy number variations (CNVs) were classified as benign, likely benign, variants of uncertain significance (VUS), likely pathogenic, and pathogenic according to American College of Medical Genetics and Genomics guidelines. The clinical findings of the some patients and the literature data were compared. Results: In 109 (24. 5%) of 445 patients, a total of 163 CNVs with reporting criterion feature were detected. Sixty-nine (42%) and 8 (5%) of these were evaluated as pathogenic and likely pathogenic, respectively. Fifteen (9%) CNVs were also evaluated as VUS. Pathogenic or likely pathogenic CNVs were detected in 61 (13. 6%) of 445 patients. Conclusions: We found that the probability of elucidating the etiology of microarray method in autism spectrum disorder, intellectual disability, and multiple congenital anomalies is 13.6% with a percentage similar to the literature. We suggest that the MYT1L, PXDN, TPO, and AUTS2 genes are all strong candidate genes for autism spectrum disorders. We detailed the clinical findings of the cases and reported that some CNV regions in the genome may be associated with autism.
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    Distal 3p Duplication and 22q13.3 Deletion with Severe Hypotonia Originating from a Paternal Balanced Translocation (3;22)
    (Karger, 2020) Yalcintepe, Sinem; Atli, Emine I.; Atli, Engin; Demir, Selma; Ciftdemir, Nukhet A.; Duran, Ridvan; Ozdemir, Janset
    In this study, we present a case with distal 3p duplication and 22q13.3 deletion due to unbalanced meiotic segregation in her father carrying a balanced translocation. The 2-month-old girl was examined for her severe hypotonia, developmental delay, and mild dysmorphic appearance. Clinical features include broad forehead, hypertelorism, laterally extended eyebrows, long eyelashes, a depressed nasal root, bifid nasal tip, long philtrum, thin lips, posteriorly rotated ears, short neck, partial syndactyly of the right hand (fingers 3, 4) , and partial syndactyly of the right foot (toes 2, 3). After examination, the final karyotype was reported as: 46,XX,der(22)del(22)(qter)dup(3)(p22pter), and the array-CGH results showed arr[GRCh37] 3p26.3p22.1(93949_41518607)x3 and arr[GRCh37] 22q13.31q13.33(44554083_51224252)x1. The mother has a 46,XX karyotype, and her father carries a balanced translocation, 46,XY,t(3;22)(p26.3;q13.3). This is the first case with a distal 3p duplication and 22q13.3 deletion with severe hypotonia and developmental delay.
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    EFFECTS OF CHROMOSOMAL TRANSLOCATIONS ON SPERM COUNT IN AZOOSPERMIC AND OLIGOSPERMIC CASES
    (Dokuz Eylul Univ Inst Health Sciences, 2022) Ayaz, Akif; Yalcintepe, Sinem; Ozalp, Ozge; Gulec, Elif Yilmaz; Gezdirici, Alper; Akcay, Ebru Perim; Koseoglu, Abdullah Huseyin
    Purpose: A number of mechanisms have been proposed for the effect of chromosomal translocations on spermatogenesis and sperm maturation. However, there are still numerous ambiguous issues regarding these two processes. The aim of this study is to evaluate the effect of chromosome break areas on sperm count in the light of the literature. Material and Methods: The study was conducted on the data of 16 male patients with reciprocal or Robertsonian translocation among 152 patients who were admitted to Adana Numune Training and Research Hospital and Kanuni Sultan Suleyman Training and Research Hospital Genetic Diagnosis Centers between 2013 and 2016 due to azoospermia and oligospermia. Results: 11 of these patients had reciprocal and five patients had Robertsonian translocations. All the patients with Robertsonian translocations were detected with azoospermia. Of the patients with reciprocal translocation, five of them were azoospermic and six of them were severe oligospermic. Conclusion: A total of 21 chromosomal breakpoints were identified in the 11 patients with reciprocal translocations. These chromosomal breakpoints may contribute to the clarification of ambiguous issues related to spermatogenesis and sperm maturation. The results also showed the importance of genetic counselling in patients with translocations.
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    First Report of Jacobsen Syndrome with Dextrocardia Diagnosed with del(11)(q24q25)
    (Karger, 2022) Yalcintepe, Sinem; Zhuri, Drenushe; Sezginer Guler, Hazal; Atli, Engin; Demir, Selma; Atli, Emine Ikbal; Mail, Cisem
    Jacobsen syndrome is a rare congenital disorder that is caused by the deletion of several genes in chromosome 11. A 10-year-old female with congenital heart disease, dextrocardia, and coarse facial appearance was examined in our medical genetics clinic. Chromosome analysis and array-CGH showed a copy number loss of 9 Mb in the 11q24.2q25 region. Herein, we report her clinical findings. This is the first case of Jacobsen syndrome with dextrocardia.
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    The Frequency of SMN1, SMN2 Copy Numbers in 246 Turkish Cases Analyzed with MLPA Method
    (Thieme Medical Publ Inc, 2023) Yalcintepe, Sinem; Karal, Yasemin; Demir, Selma; Atli, Emine Ikbal; Atli, Engin; Eker, Damla; Mail, Cisem
    This study aimed to define the copy numbers of SMN1 and SMN2 genes and the diagnosis rate and carrier frequency of spinal muscular atrophy (SMA) in the Thrace region of Turkey. In this study, the frequency of deletions in exons 7 and 8 in the SMN1 gene and SMN2 copy numbers were investigated. A total of 133 cases with the preliminary diagnosis of SMA and 113 cases with the suspicion of being an SMA carrier from independent families were analyzed by multiplex ligation-dependent probe amplification method for SMN1 and SMN2 gene copy numbers.SMN1 homozygous deletions were detected in 34 patients (25.5%) of 133 cases with the suspicion of SMA. Cases diagnosed with SMA type I was 41.17% (14/34), 29.4% (10/34) with type II, 26.4% (9/34) with type III, and 2.94% (1/34) with type IV. The SMA carrier rate was 46.01% in 113 cases. In 34 SMA cases, SMN2 copy numbers were: two copies - 28 cases (82.3%), three copies - 6 cases (17.6%). SMN2 homozygous deletions were detected in 15% (17/113) of carrier analysis cases. The consanguinity rate of the parents was 23.5% in SMA diagnosed cases. In this study, we had a 25.5% of SMA diagnosis rate and 46% SMA carrier frequency. The current study also showed the relatively low consanguinity rate of the Thrace region, with 23.5% according to the east of Turkey.
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    THE FREQUENCY OF Y CHROMOSOME MICRODELETIONS AND CYTOGENETIC ABNORMALITIES IN CASES WITH MALE INFERTILITY FROM THRACE REGION: SINGLE CENTER EXPERIENCE
    (Istanbul Univ, Fac Medicine, Publ Off, 2021) Yalcintepe, Sinem; Eker, Damla; Gurkan, Hakan
    Objective: Genetic factors, including Y chromosome microdeletions, are responsible for about 10% of male infertility cases and are particularly associated with azoospermia or severe oligozoospermia. In our study, it was aimed to determine the frequency of Y chromosome microdeletions in the Thrace region and to provide information about the heterogeneous phenotype in infertile male patients with AZF microdeletion. Material and Method: Chromosome analysis and Y chromosome microdeletion analysis were performed on 446 male patients with non-obstructive azoospermia or oligozoospermia, who applied to the Trakya University Hospital Medical Genetics Department Genetic Diseases Diagnosis Center clinic between the years 2011-2019. Results: Y chromosome microdeletion was detected in 19 (4.26%) of 446 cases. Structural chromosomal anomalies were accompanied in 5 of 19 cases with Y chromosome microdeletions. Three hundred fifty-two cases had no Y chromosome microdeletion, 35 (9.94%) of these cases had Klinefelter syndrome, 1 (0.28%) case had Klinefelter syndrome low grade mosaicism, 3 (0.85%) cases had Robertsonian translocation carriage, and 1 (0.28%) had Reciprocal translocation carriage. Conclusion: Y chromosome microdeletion screening in non-obstructive azoospermic or oligosoospermic infertile male patients has prognostic value and affects clinical prognosis. The results of our study support the proposal to perform Y chromosome microdeletion analysis before microTESE in azoospermic or oli-gosoospermic infertile male patients as reported in the literature.
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    Genetic screening results of individuals with high risk BRCA-related breast/ovarian cancer in Trakya region of Turkey
    (Imprimatur Publications, 2020) Demir, Selma; Tozkir, Hilmi; Gurkan, Hakan; Atli, E. Ikbal; Yalcintepe, Sinem; Atli, Engin; Sezer, Y. Atakan
    Purpose: Pathogenic/likely pathogenic (P/LP) germline variations in BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. This study presents the BRCA1/BRCA2 sequencing and deletion duplication analyses results of of 493 participants (485 women, 8 men) selected based on the National Comprehensive Cancer Network (NCCN) guidelines. Methods: Next generation sequencing (NGS) and multiplex ligation-dependent probe amplification methods (MLPA) were used to define germline BRCA1/BRCA2 positivity. Results: Overall, the P/LP frequency of the participants was 17.8%. Five of the likely pathogenic variants were novel. The 5266dupC pathogenic variation, which is a founder mutation in the Ashkenazi Jewish population, was the most common variation among the patients, with a frequency of 5.47%. The pathogenic/likely pathogenic variation frequency was significantly higher (p=0.01) among clinically diagnosed familial cancer patisents than those participants without personal history of cancer but enrolled for BRCA1 testing due to familial risk. BRCA1/BRCA mutation positivity was significantly higher (p=0.000) among those who had at least one first- or second-degree relative with breast/ovarian cancer from patients who had no family history. BRCA1/BRCA2 mutation positivity was 69.23% between the patients who had personal history of both breast and ovarian cancer. Conclusion: Based on our findings, we suggest that sequencing all of the coding regions of the BRCA1/BRCA2 genes using NGS is a feasible approach for individuals who are at risk of developing BRCA-related cancer according to NCCN guidelines. The 5266dupC pathogenic variation, as the most common pathogenic variation in the Trakya region of Turkey, should be included if a targeted mutatin screening is planned.
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    Genotype-phenotype correlations of pathogenic copy number variations on X chromosome detected by comparative genomic hybridization
    (Elsevier, 2022) Yalcintepe, Sinem; Atli, Engin; Atli, Emine Ikbal; Demir, Selma; Ozen, Yasemin; Mail, Cisem; Gurkan, Hakan
    The aim of this study was to present genotype-phenotype correlations of pathogenic copy number variations (CNVs) on X chromosome. Clinical and microarray data of the cases were collected. Conventional cytogenetics and CytoSure 4x180K oligonucleotide array (Agilent Technologies, Inc.) (Comparative Genomic Hybridization - CGH) was applicated to all cases. Molecular and clinical characterisation of these CNVs was performed in this study. 18 cases were included in this study for having a pathogenic CNV on X chromosome. The changes were reported pathologically by evaluating break points, anomaly size, number of involved genes and their functions and phenotypic correlations. 16 cases with pathogenic CNVs of X chromosome were examined with the clinical findings of multiple congenital anomalies, mental retardation, eosophageal atresia, duodenal atresia, autism spectrum disorder, hypogonadotropic hypogonadism, dysmorphic features, muscular dystrophy, hydrocephaly, neuromotor growth retardation, trigonocephaly, high risk of prenatal screening test, recurrent pregnancy loss with reciprocal translocation, fetal loss with multiple congenital anomalies. 2 cases were diagnosed as Turner Syndrome with rare karyotypes and array-CGH results. Our study contributes to the genotype/phenotype correlation with the delineation of laboratory criteria which help to classify the different CNVs detected on X chromosome. Atypical microdeletions/duplications allowed us to define minimal critical regions that could be responsible for specific clinical findings of the syndromes and to highlight some genes.
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    Germline Pathogenic Variants Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma
    (Codon Publications, 2021) Yalcintepe, Sinem; Gurkan, Hakan; Korkmaz, Fatma Nur; Demir, Selma; Atli, Engin; Eker, Damla; Guler, Hazal Sezginer
    The aim of this study was to evaluate germline variant frequencies of pheochromocytoma and paraganglioma targeted susceptibility genes with next-generation sequencing method. Germline DNA from 75 cases were evaluated with targeted next-generation sequencing on an Illumina NextSeq550 instrument. KIF1B. RET, SDHB, SDHD, TMEM127, and VHL genes were included in the study, and Sanger sequencing was used for verifying the variants. The pathogenic/likely pathogenic variants were in the VHL, RET, SDHB, and SDHD genes, and the diagnosis rate was 24% in this study. Three different novel pathogenic variants were determined in five cases. This is the first study from Turkey, evaluating germline susceptibility genes of pheochromocytoma and paraganglioma with a detection rate of 24% and three novel variants. All patients with pheochromocytoma and paraganglioma need clinical genetic testing with expanded targeted gene panels for higher diagnosis rates.
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    Homozygous Paternally Inherited ASPA Variant in a Patient with Canavan Disease
    (Karger, 2024) Yalcintepe, Sinem; Maras, Tuba; Kizilyar, Ilke; Guler, Hazal Sezginer; Zhuri, Drenushe; Atli, Engin; Ozen, Yasemin
    Introduction: Canavan disease is an autosomal recessive disorder that causes accumulation of N-acetyl ASPArtic acid in the brain due to ASPArtoacylase deficiency with homozygous or compound heterozygous pathogenic variants in the ASPA gene located on the short arm of chromosome 17. Clinical findings are hypotonia, progressive macrocephaly, deafness, nystagmus, blindness, and brain atrophy. Case Presentation: A one-year-old female case was evaluated in our medical genetics clinic for hypotonia, nystagmus, and strabismus. Chromosome analysis and array-comparative genomic hybridization showed no pathology. Clinical exome sequencing by next-generation sequencing was performed and a homozygous likely pathogenic variant NM_000049.4(ASPA):c.857C > A p.(Ala286Asp) was identified. Sanger sequencing of the parents showed that the index case had a homozygous genotype, the father was heterozygous and the mother had a wild genotype for the identified variant in ASPA. A single nucleotide polymorphism (SNP) array test was planned for the family to explain this homozygosity and a loss of maternal heterozygosity was determined in the 17p13.3-p13.2 region of the ASPA gene. Conclusion: In this report, we aimed to present the first case of Canavan disease with maternal loss of heterozygosity in the ASPA gene. (c) 2024 S. Karger AG, Basel
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    Identification of a Novel KIF11 Variant p.(Leu804Thrfs Ter13) in a Case with Isolated Microcephaly
    (Wolters Kluwer Medknow Publications, 2022) Yalcintepe, Sinem; Guler, Hazal Sezginer; Zhuri, Drenushe; Eker, Damla; Gurkan, Hakan
    Microcephaly is a rare neurological condition, and it is characterized by a smaller head than other children of the same age and sex. Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MLCRD) is a syndrome with a varying spectrum that occurs as a result of variants of KIF11 gene. A 3-year-old girl was presented to our clinic with microcephaly; she had no motor or growth retardation except microcephaly. After obtaining a normal karyotype and microarray result, Trusight One-Expanded Panel analysis showed NM_004523.4 (KIF11): c. 2409dupA (p. Leu804Thrfs Ter13) heterozygous pathogenic novel variant. Patients who have KIF11 mutation often also have different clinical features; in our case, the motor development is consistent with its peers and has a history of prenatal and postnatal microcephaly. Microcephaly can be caused by a variety of genetic mutations. In our case, firstly we identify the association of a novel de novo KIF11 gene duplication variant related to isolated microcephaly.