A Case Report of SYNE1 Deficiency-Mimicking Mitochondrial Disease and the Value of Pangenomic Investigations

Mitochondrial disorders are characterized by a huge clinical, biochemical, and genetic heterogeneity, which poses significant diagnostic challenges. Several studies report that more than 50% of patients with suspected mitochondrial disease could have a non-mitochondrial disorder. Thus, only the iden...

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Bibliographic Details
Published in:Genes 2023-11, Vol.14 (12), p.2154
Main Authors: Serag, Mounir, Plutino, Morgane, Charles, Perrine, Azulay, Jean-Philippe, Chaussenot, Annabelle, Paquis-Flucklinger, Véronique, Ait-El-Mkadem Saadi, Samira, Rouzier, Cécile
Format: Article
Language:English
Subjects:
Ataxia
Biopsy
Case reports
Cerebellar ataxia
Cerebellum
Copy number
Disease
Families & family life
Genes
Genomes
Genotype & phenotype
Histology
Hybridization
Mitochondria
Mitochondrial DNA
Neuromuscular diseases
Patients
Phenotypes
Thermal cycling
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Summary:Mitochondrial disorders are characterized by a huge clinical, biochemical, and genetic heterogeneity, which poses significant diagnostic challenges. Several studies report that more than 50% of patients with suspected mitochondrial disease could have a non-mitochondrial disorder. Thus, only the identification of the causative pathogenic variant can confirm the diagnosis. Herein, we describe the diagnostic journey of a family suspected of having a mitochondrial disorder who were referred to our Genetics Department. The proband presented with the association of cerebellar ataxia, COX-negative fibers on muscle histology, and mtDNA deletions. Whole exome sequencing (WES), supplemented by a high-resolution array, comparative genomic hybridization (array-CGH), allowed us to identify two pathogenic variants in the non-mitochondrial gene. The proband and her affected sister were found to be compound heterozygous for a known nonsense variant (c.13258C>T, p.(Arg4420Ter)), and a large intragenic deletion that was predicted to result in a loss of function. To our knowledge, this is the first report of a large intragenic deletion of in patients with cerebellar ataxia (ARCA1). This report highlights the interest in a pangenomic approach to identify the genetic basis in heterogeneous neuromuscular patients with the possible cause of mitochondrial disease. Moreover, even rare copy number variations should be considered in patients with a phenotype suggestive of SYNE1 deficiency.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes14122154