Genetic Variants Linked to Dyslexia Co-Morbid ADHD: A Case Study of a Pakistani Outpatient
Main Article Content
Keywords
Dyslexia , ADHD , Whole Exome sequencing , Pathway analysis
Abstract
Developmental Dyslexia (DD) and Attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders that often coexist and share complex genetic underpinnings. Our case study integrates psychological assessments and whole exome sequencing to explore the genetic basis of DD and ADHD co-occurrence in a single proband (a nine-year-old female born healthy) from a consanguineous Pakistani family. We present a proband with symptoms of impulsivity, inattention, and severe hyperactive behavior, along with speech impairment and moderate learning disabilities. The study identified non-synonymous gene variations associated with both disorders, such as COMT, ADRA1A, HTR2A, DNAAF4, DCDC2, KIAA0319, LRRC56, and PHRF1. Network analysis revealed key pathways like S100 Family Signaling, G-Protein Coupled Receptor Signaling, and Dopamine Receptor Signaling shedding light on potential mechanisms underlying the observed phenotypes. The study emphasizes the complexity of these conditions and underscores the need for personalized interventions to address diagnosis challenges.
References
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2. Slaby, R. J.; Arrington, C. N.; Malins, J.; Sevcik, R. A.; Pugh, K. R.; Morris, R. Properties of white matter tract diffusivity in children with developmental dyslexia and comorbid attention-deficit/hyperactivity disorder. J NeurodevDisord. 2023, 15(1), 25.
3. Serrallach, B.; Groß, C.; Bernhofs, V.; Engelmann, D.; Benner, J.; Gündert, N.; Blatow, M.; Wengenroth, M.; Seitz, A.; Brunner, M.; Seither, S.; Parncutt, R.; Schneider, P.; Seither-Preisler, A. Neural Biomarkers for Dyslexia, ADHD, and ADD in the Auditory Cortex of Children. Front Neurosci.2016, 10, 324.
4. Karalunas, S. L.; Hawkey, E.; Gustafsson, H.; Miller, M.; Langhorst, M.; Cordova, M.; Fair, D.; Nigg, J. T. Overlapping and Distinct Cognitive Impairments in Attention-Deficit/Hyperactivity and Autism Spectrum Disorder without Intellectual Disability. J Abnorm Child Psychol. 2018, 46(8), 1705-1716.
5. Wang, L.J.; Yu, Y.H.; Fu, M.L.; Yeh, W.T.; Hsu JL, Yang, Y.H.; Yang, H.T.; Huang, S.Y.; Wei, I.L.; Chen, W.J.; Chiang, B.L.; Pan, W.H. Dietary Profiles, Nutritional Biochemistry Status, and Attention-Deficit/Hyperactivity Disorder Path Analysis for a Case-Control Study. J Clin Med. 2019, 8(5), 709.
6. Wagner, R.K.; Zirps, F.A.; Edwards, A.A.; et al. The Prevalence of Dyslexia: A New Approach to Its Estimation. J Learn Disabil. 2020, 53(5), 354-365.
7. Chung, W.; Jiang, S.F.; Paksarian. D.; et al. Trends in the Prevalence and Incidence of Attention-Deficit/Hyperactivity Disorder Among Adults and Children of Different Racial and Ethnic Groups. JAMA Netw Open. 2019, 2(11), e1914344.
8. Ashraf, A.; Tohid, H. The Lack of Trained Child Psychiatrists Leading to Underreported Cases of ADHD in Pakistan. J Cell Sci Ther. 2016, 7, e125
9. Ibrahim, M.; Saeed Ullah, Jan. Bibliometric analysis of the Journal of Pakistan Medical Association form 2009 to 2013. J Pak Med Assoc. 2015, 65(9), 978-983.
10. Jalkh, N.; Corbani, S.; Haidar, Z.; et al. The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population. BMC Med Genomics. 2019, 12(1), 11.
11. Chong, J.X.; Buckingham, K.J.; Jhangiani, S.N.; et al. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. Am J Hum Genet. 2015, 97(2):199-215.
12. Rabbani, B.; Tekin, M.; Mahdieh, N. The promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014, 59(1), 5-15.
13. Retterer, K.; Juusola, J.; Cho, M.T.; et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med. 2016, 18(7), 696-704.
14. Wright, C.F; Fitzpatrick, D.R.; Firth, H.V. Paediatric genomics: diagnosing rare disease in children [published correction appears in Nat Rev Genet. 2018 Feb 19;]. Nat Rev Genet. 2018, 19(5), 253-268.
15. American Psychiatric Association, D. S. M. T. F.; American Psychiatric Association; Diagnostic and statistical manual of mental disorders. 2013, DSM-5 (Vol. 5, No. 5). Washington, D; American psychiatric association.
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17. Jaffar, R.; Ali, A. Z. USING URDU-ENGLISH CODE-SWITCHING IN THE TRANSLATION OF SLOSSON INTELLIGENCE TEST. Pakistan Journal of Educational Research. 2021, 4(4).
18. Reynolds, M. R.; Niileksela, C. R. Test Review: Schrank, F.A.; McGrew, K.S.; Mather, N. 2015. Woodcock-Johnson IV Tests of Cognitive Abilities.
19. Schrank, F. A.; Wendling, B. J. The Woodcock–Johnson IV: Tests of cognitive abilities, tests of oral language; tests of achievement. In D. P. Flanagan & E. M. McDonough (Eds.), Contemporary intellectual assessment: Theories, tests, and issues. 2018 , pp. 383–451. The Guilford Press.
20. Conners, C.K. Rating scales in attention-deficit/hyperactivity disorder: use in assessment and treatment monitoring. J Clin Psychiatry. 1998, 59 Suppl 7, 24-30.
21. Conners, C.K.; Sitarenios, G.; Parker, J.D.; Epstein, J.N. The revised Conners' Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity. J Abnorm Child Psychol. 1998, 26(4), 257-268.
22. Cerminara, M.; Spirito, G.; Pisciotta, L.; et al. Case Report: Whole Exome Sequencing Revealed Disease-Causing Variants in Two Genes in a Patient with Autism Spectrum Disorder, Intellectual Disability, Hyperactivity, Sleep and Gastrointestinal Disturbances. Front Genet. 2021, 12:625564.
23. Chen, S.; Huang. T.; Zhou, Y.; Han, Y.; Xu, M.; Gu, J. After QC: automatic filtering, trimming, error removing and quality control for fastq data. BMC Bioinformatics. 2017, 18(Suppl 3):80.
24. Richards, S.; Aziz, N.; Bale, S.; et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015, 17(5), 405-424.
25. Venselaar, H.; Te Beek, T.A.; Kuipers, R.K.; Hekkelman, M.L.; Vriend, G. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC Bioinformatics. 2010, 11:548.
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28. Attention-Deficit/Hyperactivity Disorder (AD/HD) and Dyslexia. https://dyslexiaida.org/attention-deficithyperactivity-disorder-adhd-and-dyslexia/. (accessed on 08/14/2023).
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30. Sharif, M.R; Madani, M.; Tabatabaei, F.; Tabatabaee, Z. The Relationship between Serum Vitamin D Level and Attention Deficit Hyperactivity Disorder. Iran J Child Neurol. 2015, 9(4), 48-53.
31. Qayyum, A.; Zai, C.C.; Hirata, Y.; et al. The Role of the Catechol-o-Methyltransferase (COMT) GeneVal158Met in Aggressive Behavior, a Review of Genetic Studies. Curr Neuropharmacol. 2015, 13(6), 802-814.
32. Kereszturi, E.; Tarnok, Z.; Bognar, E.; et al. Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am J Med Genet B Neuropsychiatr Genet. 2008, 147B(8), 1431-1435.
33. Kabukcu, B.B.; Buber, A.; Basay, O.; et al. White matter alterations related to attention-deficit hyperactivity disorder and COMT val158met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus), Neuropsychiatric disease and treatment. 2016, 969-981.
34. Gallaway, K.A.; Skaar, T.C.; Biju, A.; Slaven, J.; Tillman, E.M. A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients. Pharmacotherapy. 2022, 42(6),453-459.
35. Yang, L.; Qian, Q.; Liu, L.; Li, H.; Faraone, S.V.; Wang, Y. Adrenergic neurotransmitter system transporter and receptor genes associated with atomoxetine response in attention-deficit hyperactivity disorder children. J Neural Transm (Vienna). 2013, 120(7), 1127-1133.
36. Roman, T.; Polanczyk, G.V.; Zeni, C.; Genro, J.P.; Rohde, L.A.; Hutz, M.H. Further evidence of the involvement of alpha-2A-adrenergic receptor gene (ADRA2A) in inattentive dimensional scores of attention-deficit/hyperactivity disorder. Mol Psychiatry. 2006, 11(1), 8-10.
37. Cheon, K.A.; Cho, D.Y.; Koo, M.S.; Song, D.H.; Namkoong, K. Association between homozygosity of a G allele of the alpha-2a-adrenergic receptor gene and methylphenidate response in Korean children and adolescents with attention-deficit/hyperactivity disorder. Biol Psychiatry. 2009, 65(7), 564-570.
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Sep 22, 2024
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Shujjah Haider, Tanmoy Mondal, Irum Nawaz, MaleehaAzam, & Somiranjan Ghosh. (2024). Genetic Variants Linked to Dyslexia Co-Morbid ADHD: A Case Study of a Pakistani Outpatient. Journal of Population Therapeutics and Clinical Pharmacology, 31(9), 2698-2711. https://doi.org/10.53555/rd5d9s46
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Author Biographies
Shujjah Haider
Translational Genomic Laboratory, Department of Bioscience, COMSATS University Islamabad, 45550, Pakistan
Tanmoy Mondal
Department of Biology, Howard University, Washington DC 20059, USAsIrum Nawaz
Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Islamabad, 46000 Pakistan
MaleehaAzam
Translational Genomic Laboratory, Department of Bioscience, COMSATS University Islamabad, 45550, Pakistan
Somiranjan Ghosh
Departments of Pediatrics and Child Health, College of Medicine, Howard University,
How to Cite
Shujjah Haider, Tanmoy Mondal, Irum Nawaz, MaleehaAzam, & Somiranjan Ghosh. (2024). Genetic Variants Linked to Dyslexia Co-Morbid ADHD: A Case Study of a Pakistani Outpatient. Journal of Population Therapeutics and Clinical Pharmacology, 31(9), 2698-2711. https://doi.org/10.53555/rd5d9s46