Genetic diversity in hereditary axonal neuropathy: Analyzing 53 Brazilian children.

Autor: Figueiredo FB; Neuroscience and Behavior Sciences Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil., Tomaselli PJ; Neuroscience and Behavior Sciences Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil., Hallak J; Neuroscience and Behavior Sciences Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.; National Institute of Sciences and Technology-INCT-Translational Medicine-CNPq/FAPESP, Ribeirao Preto, Brazil., Mattiello-Sverzut AC; Health Science Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil., Covaleski APPM; Neurology Department, Federal University of Pernambuco, Recife, Brazil., Sobreira CFDR; Neuroscience and Behavior Sciences Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil., de Paula Gouvêa S; Neuroscience and Behavior Sciences Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil., Marques W Jr; Neuroscience and Behavior Sciences Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.; National Institute of Sciences and Technology-INCT-Translational Medicine-CNPq/FAPESP, Ribeirao Preto, Brazil.
Jazyk: angličtina
Zdroj: Journal of the peripheral nervous system : JPNS [J Peripher Nerv Syst] 2024 Mar; Vol. 29 (1), pp. 97-106. Date of Electronic Publication: 2024 Feb 20.
DOI: 10.1111/jns.12617
Abstrakt: Background and Aims: The genetic epidemiology of inherited neuropathies in children remains largely unknown. In this study, we specifically investigated the genetic profile of a Brazilian cohort of pediatric patients with pure or complex axonal neuropathies, a crucial knowledge in the near future for establishing treatment priorities and perspectives for this group of patients.
Methods: Fifty-three pediatric patients who were assessed prior to reaching the age of 20, and who had clinical diagnoses of axonal hereditary neuropathy or presented with axonal neuropathy as the primary clinical feature, were included in the study. The recruitment of these cases took place from January 1, 2018, to December 31, 2020. The diagnosis was based on clinical and electrophysiological data. A molecular assessment was made using target-gene panel or whole-exome sequencing. Subsequently, segregation analysis was performed on available family members, and all candidate variants found were confirmed through Sanger.
Results: A molecular diagnosis was reached in 68% of the patients (n = 36/53), considering only pathogenic and probably pathogenic variants. Variants in MFN2 (n = 15) and GJB1 (n = 3) accounted for half of the genetically confirmed patients (50%; n = 18/36). The other 18 genetically diagnosed patients had variants in several less common genes.
Interpretation: Apart from MFN2 and GJB1 genes, universally recognized as a frequent cause of axonal neuropathies in most studied population, our Brazilian cohort of children with axonal neuropathies showed an important genetic heterogeneity, probably reflecting the multi ethnicity of the Brazilian population. Diagnostic, counseling, and future interventions should consider this characteristic.
(© 2024 Peripheral Nerve Society.)
Databáze: MEDLINE
Externí odkaz: