Engin ATLI,
Isik GORKER,
Sinem YALCINTEPE,
Cisem MAİL,
Hakan GÜRKAN,
Emine İkbal ATLİ,
Leyla BOZATLI,
Mengühan ARAZ ALTAY,
Damla EKER,
Selma DEMİR,
Hasan Cem AYKUTLU
7217
Investigation the etiology of syndromic autism with targeted gene analysis
Investigation the etiology of syndromic autism with targeted gene analysis
Aim: In this study, we aimed to determine the etiology of syndromic autism with analyzing 50 genes with a targeted gene panel. Cases with a pre-diagnosis of genetic syndrome including autism spectrum disorder were analysed in the current study. Materials and Methods: The targeted gene panel containing fifty genes causing syndromic autism was sequenced using the Illumina NextSeq550 platform. Forty-nine cases with autism spectrum disorder and syndromic clinical findings were analysed after excluding chromosomal abnormalities, microdeletion/duplication syndromes and Fragile X syndrome. Results: Pathogenic/likely pathogenic variants or variants of unknown clinical significance were detected in 26.5% (13/49) of the cases. One case was diagnosed with KBG Syndrome with a de novo pathogenic variant detected in the ANKRD11 gene. Other two pathogenic/likely pathogenic variants were detected in DHCR7 and AMT genes, two cases were accepted as carriers for these genes. Eleven variants of unknown clinical significance were detected in the VPS13B, SETD2, DHCR7, GRIP1, MED12, ALDH5A1, CREBBP, NSD1 and CHD7 genes. Conclusion: In this study, the diagnosis rate was 2%, and the rate of pathogenic/likely pathogenic variant detection rate was 6%, after excluding the cases diagnosed with microdeletion/duplication syndromes and Fragile X Syndrome. Our study is the first study in the literature with 50 genes targeted panel investigating the association of autism spectrum disorder and syndromic disorders with high phenotypic diversity.
___
- 1. First MB, Gaebel W, Maj M, et al. An organization- and category-level comparison of diagnostic requirements for mental disorders in ICD-11 and DSM-5. World Psychiatry 2021;20:34-51.
- 2. Brignell A, Chenausky KV, Song H, et al. Communication interventions for autism spectrum disorder in minimally verbal children. Cochrane Database Syst Rev 2018;11:CD012324.
- 3. Stefanatos GA. Regression in autistic spectrum disorders. Neuropsychol Rev 2008;18:305-19. 4. Herman GE, Henninger N, Ratliff-Schaub K, et al. Genetic testing in autism: how much is enough? Genet Med 2007;9:268-74.
- 5. Filice F, Janickova L, Henzi T, et al. The Parvalbumin Hypothesis of Autism Spectrum Disorder. Front Cell Neurosci 2020;14:577525.
- 6. Carter MT, Scherer SW. Autism spectrum disorder in the genetics clinic: a review. Clin Genet 2013;83:399- 407.
- 7. Neale BM, Kou Y, Liu L, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012;485:242-5.
- 8. Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012;485:237-41.
- 9. Kim SJ, Yang A, Park JS, et al. Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review. Front Genet 2020;11:579805.
- 10. Herrmann J, Pallister PD, Tiddy W, et al. The KBG syndrome-a syndrome of short stature, characteristic facies, mental retardation, macrodontia and skeletal anomalies. Birth Defects Orig Artic Ser 1975;11:7-18.
- 11. Ockeloen CW, Willemsen MH, de Munnik S, et al. Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations. Eur J Hum Genet. 2015;23:1176-85.
- 12. Skjei KL, Martin MM, Slavotinek AM. KBG syndrome: report of twins, neurological characteristics, and delineation of diagnostic criteria. Am J Med Genet A 2007;143A:292-300.
- 13. Low K, Ashraf T, Canham N, et al.; DDD Study, Smithson S. Clinical and genetic aspects of KBG syndrome. Am J Med Genet A 2016;170:2835-46.
- 14. Zhang T, Yang Y, Yin X, et al. Two loss-of-function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway. Am J Med Genet A 2021;185:710-8.
- 15. Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008;9:341-55. Erratum in: Nat Rev Genet 2008;9:493.
- 16. Inci A, Ozaslan A, Okur I, et al. Autism: Screening of inborn errors of metabolism and unexpected results. Autism Res 2021.
- 17. Posar A, Visconti P. Syndromic Autism Spectrum Disorder: Let Us Not Forget about Succinic Semialdehyde Dehydrogenase Deficiency. A Case Report with Literature Review. J Pediatr Neurosci 2020;15:297-300.