Investigation of DCDC2 and DYX1C1 genes using next generation sequencing analysis in patients diagnosed with specific learning disorders

Aim: Specific Learning Disorder (SLD) is one of the common neurodevelopmental disorders in childhood. As far as we know, there is no study investigating the relationship between SLD and DYX1C1 and DCDC2 genes by investigating the whole gene with the next generation sequence analysis (NGS) method. This study is intended to be the first study to investigate the DYX1C1 and DCDC2 genes in children diagnosed with SLD in Turkish society by using the NGS method. Material and Methods: A group of patients between the ages of 6-12 who were diagnosed with only SLD (n=12) and diagnosed with SLD plus attention deficit and hyperactivity disorder (ADHD) (n=45) according to DSM-V and and the control group (n=48) who at the same age / class, did not have any psychiatric disorder and volunteered to participate included in the study. The SLD test battery and the WISC-R test were applied separately in the patient and control groups in order to evaluate the symptoms of SLD in detail, and to determine the level of intelligence, respectively. " The Schedule for Affective Disorders and Schizophrenia (SADS) for School-Age Children – Present and Lifetime Version (K-SADS-PL)" was conducted in the patient and control groups for additional psychiatric diagnosis screening interview and to determine the current level of function of the child. In order to help exclude additional diagnoses, ''The Screen for Child Anxiety Related Disorders (SCARED)'' and The Children's Depression Rating Scale (CDRS)'' were applied. "Learning Disorder Symptom Screening List" and "Screening and Evaluation Scale Based on DSM-IV for Disruptive Behavior Disorders" were given to the parents / teachers of both groups. DYX1C1 and DCDC2 genes were screened by the NGS analysis method after genomic DNA isolation from peripheral venous blood samples taken from the residual blood of the study participants. The data obtained as a result of scanning were statistically analyzed. Results: DYX1C1 gene variations have been associated with SLD in individual comparison (p = 0.029), however, according to the presence or absence of variations, the relationship with SLD was not found (p = 0.247). No relation with SLD was found when we look at both individual comparisons of DCDC2 gene variations and whether there are variations. Considering the variations in the genes, only 572A> G variation from the DYX1C1 gene was significantly higher in the control group, while the 1249G> T variation was significantly higher in the patient group. For the DCDC2 gene, only 426-13C> T variation was as significantly higher in the control group. In comparing the variations with the clinical picture; 572A> G variation in the DYX1C1 gene was associated with better performance in the number of words read in one minute, reading speed, calculation from mind, collection, questioning the prior-after-months relationship in months, alphabetical and rhythmic counting test, gesell and clock drawing subtests. In addition, this variation was related to make fewer mistakes in the types of errors such as letter jumping, syllable jumping, adding letters, adding syllables, adding words, reading by matching the end of the word in reading test; in the types of letters that you hear, skip, syllable, inverse write and letter mixing error types, in the type of sight you see in the syllable error type, in the free writing section, and syllable error type. The 1249G> T variation was found to be associated with lower performance in the number of words read per minute, reading speed, questioning the priority-post relationship in months, in alphabetical order subtests and judgment test in WISC-R test. In addition, this variation was associated with making more mistakes in reading, especially reading syllables, adding letters, adding syllables. It was found that the 271G> A variation was related to more frequent errors in the type of letter jump error in the write test, the letter jump in the free write test, and the type of error in the letter mixing error type, and related to poor performance in the lateralization test. In DCDC2 gene, it was found that 426-13C> T variation was related to better performance in collection questions, questioning priority-after-days relationships, clock drawing subtests and WISC-R password subtest in patient groups. In addition, it has been observed that in the reading test, it was related to adding words, matching the end of the word, reading the word type of error in the writing section of the hearing, and spelling error in the free writing section, word jumping, mixing letters, adding letters, and making less mistakes in the types of writing errors. 661A> G variation was found to be related to more errors in reading and performance, general knowledge, arithmetic, and lower performance in password subtest in WISC-R test. The 183C> T variation was related to lower performance in mind calculation skills, and in WISC-R image editing subtest. The 3C> G variation was found as associated with lower performance in the WISC-R password subtest. The 1017C> T variation was found as associated with lower performance in addition questions. Conclusion: The larger-scale studies are needed to confirm and extend our results towards 572A> G and 426-13C> T variations can be protective, and 1249G> T, 271G> A, 661A> G, 183C> T, 3C> G and 1017C> T variations may be risky for SLD in Turkish population.