Year: 2021
Type: dissertation
Study design: Observational Study
Abstract: Cerebral palsy (CP) is a result of neurological dysfunctions that do not worsen \nwith age but will be manifested as muscle impairments till adulthood. Some CP risk \nfactors are intrauterine infection, brain malformation, instrumental delivery, etc. that \noccur at three different events (antenatal, intrapartum and postpartum). Meanwhile, \nidiopathic CP refers to CP cases with unknown risk factors. This exploratory study \nwith no proposed hypothesis of specific loci was carried out to explore CP genetic in \nKelantan patients with underlying genetic factors using Whole Exome Sequencing \n(WES). As opposed to other neurodevelopmental disabilities, contribution of genomic \nabnormalities to CP occurrence has not been extensively researched despite probably \naccounting for 70–80% of cases with prenatal causes. Plus, Malaysia has yet to \nestablish CP prevalence and genetic database. Therefore, identification of genomic \ncauses would improve CP causal insight in selected families. In total, 20 subjects \nconsisting of 10 CP individuals and 10 unaffected parents were analysed in the current \nstudy. The sequenced DNA samples were analysed using bioinformatics Genome \nAnalysis Toolkit (GATK) to generate all possible variants. We found 37 rare de novo \n(n=29) and inherited variants (n=8) from a total of 29 genes and classified them \naccording to American College Medical Genetic (ACMG) standard guidelines. There \nare nine central nervous system (CNS) related genes (CDKL2, CEP164, FAM104B, \nFAM163A, FXR2, KCNK18, KCNQ3, MAPRE3 and RBMX, CP is a disorder of CNS \norigin and these genetic mutations are anticipated to contribute to CNS defect. Nine \nmutated immune-related genes (COL6A6, COL7A1, CYHR1, DLL1, GPR97, HLA \nDRB1, HLA-DRB5, LYST and MUC16) are present in CP subjects only, which possibly \nindicates that CP individuals may have potential of developing immune-related \nproblems. Thus, CP may be categorized as immune dysregulation-related neurological \ndisorder. Next are three potentially immune-related mutated genes (ANKRD36, \nDNAH17 and TTC13) with unknown molecular function, but are associated with the \nimmune system. There are also eight mutated genes of other categories (ANO5, ASTE1 \nBEST3, CTBP2 CTDSP2, DCHS2, GLYR1 and KRTAP19-6). Based on the variant data \nwe hypothesize that familial genetic CP is genetically heterogenous, consisting of \ndiscovered de novo and inherited variants that may contain important predictive \ninformation on CP. This encourages future studies with bigger sample size, more \nvalidation analysis and functional characterization to further understand the \ncontribution of the related genes to CP. This could help in the future development of \nmolecular targeted drugs and CP therapeutics intervention.
Author: Nur Atikah Nor Azhar
Language: English
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3197889727