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Master Thesis

Diagnostic étiologique de la déficience intellectuelle : résultats du séquençage d’exome en trio dans une cohorte de 818 patients

Abstract : Introduction: intellectual disability (ID) is a clinically and genetically heterogeneous condition that affects 1 to 3% of the population worldwide. Recent improvements of next generation sequencing are giving rise to a drastic change in our medical approach. We present here the clinical and genetical characteristics of a large cohort of patients suffering from ID and which had a trio-based whole exome sequencing (WES). Patients and methods: 818 patients were recruited through clinical genetic and/or neuro-pediatric consultations. ID was assessed based on neuropsychological tests when available, DSM-5 classification was used otherwise. Prior to WES, DNA micro-array, Fragile-X syndrome testing and targeted-gene analysis in case of high syndromic suspicion were performed. If negative, trio-based WES was proposed. Molecular results were discussed in multidisciplinary team meetings before feed-back to patients. Results: the global diagnostic yield was 41% across all patients (338/818 patients). 41 variants were found in candidate genes and contributed to their validation as “ID genes”, rising the potential diagnostic yield to 47% (379/818 patients). Dominant variants were pre-eminent (81%) and most of them were de novo (95%) affecting 224 unique genes. Interestingly, the severity of ID had no significative effect on the diagnostic rate (mild ID, 66/180, 37% - moderate to profound ID, 108/419, 44%, p-value = 0.1997). Epilepsy and family history of ID were not identified neither as cofounding factors (p-value = 0.132 and 0.516). Conclusion: this study emphasizes the considerable genetic heterogeneity of ID and confirms the efficiency of trio-based WES for its exploration.
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Master Thesis
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Submitted on : Tuesday, February 16, 2021 - 9:51:10 AM
Last modification on : Tuesday, July 13, 2021 - 3:15:48 AM


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  • HAL Id : dumas-03142494, version 1


Thomas Courtin. Diagnostic étiologique de la déficience intellectuelle : résultats du séquençage d’exome en trio dans une cohorte de 818 patients. Médecine humaine et pathologie. 2019. ⟨dumas-03142494⟩



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