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Copyright of Gazi Medical Journal is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Autism spectrum disorder is a genetically and phenotypically heterogeneous group. Genetic studies carried out to date have suggested that both common and rare genetic variants play a role in the etiology of this disorder. In our study, we aimed to investigate the effect of FOXP2, GRIN2B, KATNAL2 and GABRA4 gene variants in the pathogenesis of autism spectrum disorder. Method: In our prospectively planned study, all exons and exon-intron junctions of FOXP2, GRIN2B, KATNAL2 and GABRA4 genes were screened by next generation sequencing analysis in 96 patients who diagnosed with autism spectrum disorder. Results: In our study, the average age was 10.1 and the male/female ratio was 75/21. Pathogenic or likely pathogenic variants were not detected in FOXP2, GRIN2B, KATNAL2 and GABRA4 genes, however, 69 intronic variants of unknown clinical significance were detected in 50 cases (52%). Among those, 26 were in the GABRA4 gene, 22 in the FOXP2 gene, 13 in the KATNAL2 gene, and 8 in the GRIN2B gene. Twenty three of these 69 variants were novel that were not previously reported in the literature. Conclusion: In our study, we could not identify a relationship between the autism spectrum disorder and FOXP2, GRIN2B, KATNAL2 and GABRA4 genes. Identifying genetic risk factors that play a role in the etiopathogenesis of autism spectrum disorder will contribute significantly to understanding the molecular mechanisms of the disease and the development of new treatment strategies. In this context, comprehensive molecular genetic studies such as whole exome or whole genome sequencing are required with higher number of cases in different populations. [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Aim: Mandibulofacial dysostosis type Guion-Almeida was characterized by microcephaly, a characteristic craniofacial appearance with upslanting palpebral fissures, microtia, preauricular and buccal tags and intellectual disability. EFTUD2 gene was found to cause a very distinct condition with phenotypic overlap with Treacher Collins syndrome, the mandibulofacial dysostosis type Guion-Almeida (MFDGA). Methods: G-banding karyotype performed using peripheral blood. TCOF1, POLR1C and POLR1D genes associated with Treacher Collins syndrome were studied by NGS method. Chromosomal microarray analysis was performed on the proband and her parents using Agilent Technologies 4x180K SurePrint G3 Human CGH+SNP Platform. Results: A 5 years old female referred us with Treacher Collins syndrome. She was born at 37th weeks of gestation with CS as weight 3200g. Her parents were nonconsanguineous and healthy. She had a 10 years old healty brother. The patient had speech delay, history of 4-5 seizures, convulsion and hypotonia. She had a dysmorphic features including long philtrum, broad nasal bridge, broad nasal root, bulbous nose, short neck, dysplastic ear, low nape hairline, micrognathia/retrognathia. The echocardiogram revealed as normal, cranial MR revealed arachnoid cysts. Hearing test results were normal. Chromosomal analysis and NGS analysis were evaluated as normal. A 207 kb copy number variation arr[GRCh37]17q21.31(42753313-42960557)×1 was identified in our patient. Her parents arrayCGH analyses revealed as normal. Conclusion: Our array CGH finding was reported extremely rare previously. We anticipate that the findings of our patient are due to deletion of 17q21.31 and loss of function of the EFTUD2 gene. [ABSTRACT FROM AUTHOR]

An abstract of the article "Application of Next-Generation Sequencing Technology for CFTR Mutation Screening," by Selma Ulusal and colleagues is presented.

Objective: We report here the results of next-generation sequencing analysis of CFTR gene in first ten patients. Methods: Genomic DNA was isolated from blood samples of ten patients who had been referred to our center for CFTR gene mutation screening for different indications. AmpliSeq libraries were produced by using Ion Ampliseq Library Kit for coding regions (NT_007933.16) of the CFTR gene (NG_016465.3). Amplicons were enriched by using Ion PGM Template OT2 200 Kit and sequenced on Ion Torrent Personal Genome Machine by using Ion PGM Sequencing 200 Kit v2. hg19 (Genome Reference Consortium GRCh37) was used as a reference. Torrent Suite Software v4.2, VariantCaller (v4.2-r88446) and Ion Reporter Software 4.2 were used for the analysis. IGV_2.3.8 was used to visualize the sequences. Mutations were confirmed using the Sanger sequencing method. Results: There was no pathogenic mutation in five out of ten cases. There was one patient each for the following mutations: homozygous c.1521_1523delCTT, heterozygous c.1521_1523delCTT, c.3154T>G (p.Phe1052Val), and heterozygous c.3683A>G (E1228G). There was a heterozygous c.1576C>G (L526V) mutation in a patient directed to us for CFTR mutation screening before conception. Conclusion: The patient that we found to have a homozygous c.1521_1523delCTT mutation has being followed-up for cystic fibrosis. c.1576C>G (L526V) mutation that we found in the other patient was not reported in the literature before. This mutation was tested in Mutation Taster and Polyphen and it was concluded that it may have a pathogenic affect. As a result, we suggest that nextgeneration sequencing method can be used as a successful method to screen CFTR gene mutations. [ABSTRACT FROM AUTHOR]