Objectives:Advances in genetic diagnostic technology have significantly increased understanding of the genetic mechanisms underlying neurodevelopmental disorders(NDDs). However, more causative genes, as well as disease mechanisms related to NDDs, are awaiting to be discovered. Our aim is to determine the genes with disease-related variants and their pathogenetic pathways in children with NDDs, thus contribute to the elucidation of the phenotype-genotype spectrum of NDDs.
Methods:The study design was a multicentric, retrospective data-recording research. Children with NDDs including intellectual disability, autistic symptoms, unexplained motor, emotional symptoms and isolated microcephaly were recruited. Patients with defined neurometabolic/neurogenetic diseases and developmental epileptic encephalopathy(DEE) were excluded. In order to detect pathways and GO-annotations including molecular function, biological function and cell components, enrichment analysis was performed using Enrichr database (https://amp.pharm.mssm.edu/Enrichr/).
Results:Genetic test results obtained from 640 patients with NDDS in 28 pediatric neurology departments in Turkey were analyzed. After excluding candidate genes, genes associated with known neurometabolic/neurogenetic diseases and DEE, the remaining 254 genes were evaluated. The most frequent genes were MECP2,UBE3A and FOXG1, respectively. The enrichment analysis showed that the genes were predominantly associated with brain development and regulation of transcription, and they play roles in histone-lysine-N-methyltransferase activity and DNA binding. The most important pathway associated with was the lysine degradation pathway (Figures1,2).
Conclusion:Our results provide an overview of the most commonly altered genes and biological processes leading to NDDs across Turkey. While serving as a resource for the planning of national diagnostic and screening strategies, our data will also provide basis for mechanistic research in future.
Keywords: neurodevelopmental disorders, Enrichment analysis, genes
Duygu Aykol
Dokuz Eylül University School of Medicine Department of Pediatric Neurology
Turkey
Ece Sonmezler
Dokuz Eylül University School of Medicine Department of Pediatric Neurology
Turkey
Yaren Sena Hanci
Dokuz Eylül University School of Medicine Department of Pediatric Neurology
Turkey
Ayse Tosun
Adnan Menderes University, School of Medicine, Department of Pediatrics, Division of Child Neurology
Turkey
Muge Ayanoglu
Adnan Menderes University, School of Medicine, Department of Pediatrics, Division of Child Neurology
Turkey
Hande Gazeteci Tekin
Bakircay University, Pediatric Neurology, Cigli District Training Hospital
Turkey
Pinar Edem
Bakircay University, Pediatric Neurology, Cigli District Training Hospital
Turkey
Ipek Dokurel Cetin
Balikesir Atatürk Training and Research Hospital, Department of Pediatric Neurology
Turkey
Ilknur Erol
Baskent University Adana Medical and Research Center Faculty of Medicine, Division of Pediatric Neurology
Turkey
Seyda Besen
Baskent University Adana Medical and Research Center Faculty of Medicine, Division of Pediatric Neurology
Turkey
Leman Tekin Orgun
Baskent University Adana Medical and Research Center Faculty of Medicine, Division of Pediatric Neurology
Turkey
Aycan Unalp
Dr. Behcet Uz Children's Hospital, Department of Pediatric Neurology
Turkey
Unsal Yilmaz
Dr. Behcet Uz Children's Hospital, Department of Pediatric Neurology
Turkey
Muzaffer Polat
Celal Bayar University, School of Medicine, Department of Pediatric Neurology
Turkey
Tugce Aksu Uzunhan
Prof Dr Cemil Tascioglu City Hospital, Department of Pediatric Neurology
Turkey
Biray Erturk
Prof Dr Cemil Tascioglu City Hospital, Department of Pediatric Neurology
Turkey
Akif Ayaz
Istanbul Medipol University, Department of Medical Genetics
Turkey
Gulen Gul Mert
Cukurova University Faculty of Medicine Department of Pediatric Neurology
Turkey
Didem Bicer
Cukurova University Faculty of Medicine Department of Pediatric Neurology
Turkey
Akgun Olmez
Denizli Pediatric Neurology Clinic
Turkey
Ahmet Yaramis
Diyarbakir Pediatric Neurology Clinic
Turkey
Nezir Ozgun
Mardin Artuklu University, Faculty of Health Sciences, Department of Pediatric Neurology
Turkey
Sevim Turay
Duzce University Faculty of Medicine, Department of Pediatric Neurology
Turkey
Cemile Busra Olculu
Ege University Faculty of Medicine, Department of Pediatrics, Division of Child Neurology
Turkey
Ozlem Yilmaz
Ege University Faculty of Medicine, Department of Pediatrics, Division of Child Neurology
Turkey
Seda Kanmaz
Ege University Faculty of Medicine, Department of Pediatrics, Division of Child Neurology
Turkey
Serkan Kirik
Fırat University School of Medicine Department of Pediatric Neurology
Turkey
Nihal Olgac Dundar
Izmir Katip Celebi University, Department of Pediatric Neurology
Turkey
Elif Didinmez
Izmir Katip Celebi University, Department of Pediatric Neurology
Turkey
Pinar Gencpinar
Izmir Katip Celebi University, Department of Pediatric Neurology
Turkey
Cengiz Dilber
Kahramanmaras Sutcu Imam University Division of Pediatric Neurology
Turkey
Nihal Yildiz
Karadeniz Technical University Faculty of Medicine Department of Pediatric Neurology Farabi Hospital
Turkey
Elif Acar Arslan
Karadeniz Technical University Faculty of Medicine Department of Pediatric Neurology Farabi Hospital
Turkey
Ali Cansu
Karadeniz Technical University Faculty of Medicine Department of Pediatric Neurology Farabi Hospital
Turkey
Deniz Akkoyunlu Sunnetci
Kocaeli University School of Medicine, Division of Child Neurology, Department of Pediatrics
Turkey
Naci Cine
Kocaeli University School of Medicine, Department of Medical Genetics
Turkey
Tolgahan Ozer
Kocaeli University School of Medicine, Department of Medical Genetics
Turkey
Serdal Gungor
Inonu University Faculty of Medicine Turgut Ozal Research Center Department of Paediatric Neurology
Turkey
Bilge Ozgor
Inonu University Faculty of Medicine Turgut Ozal Research Center Department of Paediatric Neurology
Turkey
Gulten Ozturk
Marmara University School of Medicine Department of Pediatrics Division of Pediatric Neurology
Turkey
Yasemin Topcu
Istanbul Medipol University Faculty of Medicine Department of Pediatric Neurology
Turkey
Betul Kilic
Istanbul Medipol University Faculty of Medicine Department of Pediatric Neurology
Turkey
Kursad Aydin
Istanbul Medipol University Faculty of Medicine Department of Pediatric Neurology
Turkey
Ozlem Ersoy Kosvali
Mersin University Faculty of Medicine Departments of Pediatric Neurology
Turkey
Cetin Okuyaz
Mersin University Faculty of Medicine Departments of Pediatric Neurology
Turkey
Ayse Aksoy
Ondokuz Mayis University Division of Pediatric Neurology
Turkey
Aslihan Sari
Samsun Training and Research Hospital, Department of Pediatric Genetics, University of Health Sciences
Turkey
Deniz Yuksel
Dr Sami Ulus Maternity Child Health and Diseases Training and Research Hospital Department of Pediatric Neurology
Turkey
Abdullah Sezer
Dr Sami Ulus Maternity Child Health and Diseases Training and Research Hospital Department of Genetics
Turkey
Ergin Atasoy
Dr Sami Ulus Maternity Child Health and Diseases Training and Research Hospital Department of Pediatric Neurology
Turkey
Yasemin Karal
Trakya University Faculty of Medicine Department of Pediatric Neurology
Turkey
Emek Uyur Yalcin
Zeynep Kamil Maternity and Children's Diseases Hospital Departments of Pediatrics and Pediatric Neurology
Turkey
Nilüfer Eldes Hacihafizlioglu
Zeynep Kamil Maternity and Children's Diseases Hospital Departments of Pediatrics and Pediatric Neurology
Turkey
Yavuz Oktay
Izmir Biomedicine and Genome Center
Turkey
Uluc Yis
Dokuz Eylul University Department of Pediatric Neurology
Turkey
Hanns Lochmuller
Ottawa University Faculty of Medicine, Division of Neurology
Canada
Bulent Kara
Kocaeli University School of Medicine Department of Pediatric Neurology
Turkey
Semra Hiz Kurul
Dokuz Eylul University Department of Pediatric Neurology
Turkey
