New structural variations responsible for Charcot-Marie-Tooth disease: The first two large KIF5A deletions detected by CovCopCan software
| Autor: | Ioanna Pyromali, Sylvie Bourthoumieu, Franck Sturtz, Guilhem Solé, Paco Derouault, Mélanie Fradin, Fanny Duval, Constantin Gomes, Nesrine Benslimane, Anne-Sophie Lia, Alexandre Perani, Angélique Nizou, Frédéric Favreau, Corinne Magdelaine |
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| Přispěvatelé: | Maintenance Myélinique et Neuropathies Périphériques (MMNP), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Biochimie et Génétique Moléculaire [CHU Limoges], CHU Limoges, Hôpital Dupuytren [CHU Limoges], Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Pontchaillou [Rennes], CHU de Bordeaux Pellegrin [Bordeaux] |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Next Generation Sequencing Disease medicine.disease_cause Biochemistry Copy Number Variants Tooth disease Exon 0302 clinical medicine Structural Biology Gene duplication KIF5A Genetics CMT2 0303 health sciences Mutation Structural variations CMT Neonatal-Intractable-MYoclonus Charcot-Marie-Tooth type 2 SV Distal-Spinal-Muscular-Atrophy 3. Good health Computer Science Applications Hereditary-Spastic-Paraplegia-type-10 NGS Biotechnology Charcot-Marie-Tooth Sequence analysis CNV Biophysics Biology CovCopCan HSP10 03 medical and health sciences SNV medicine Indel Gene Structural Variant DSMA 030304 developmental biology Amyotrophic Lateral Sclerosis NEIMY Non-Allelic Homologous Recombination NAHR Single Nucleotide Variant ALS 030217 neurology & neurosurgery TP248.13-248.65 |
| Zdroj: | Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 4265-4272 (2021) Computational and Structural Biotechnology Journal Computational and Structural Biotechnology Journal, Elsevier, 2021, 19, pp.4265-4272. ⟨10.1016/j.csbj.2021.07.037⟩ |
| ISSN: | 2001-0370 |
| DOI: | 10.1016/j.csbj.2021.07.037⟩ |
| Popis: | International audience; Next-generation sequencing (NGS) allows the detection of mutations in inherited genetic diseases, like the Charcot-Marie-Tooth disease (CMT) which is the most common hereditary peripheral neuropathy. The majority of mutations detected by NGS are single nucleotide variants (SNVs) or small indels, while structural variants (SVs) are often underdiagnosed. PMP22 was the first gene described as being involved in CMT via a SV of duplication type. To date, more than 90 genes are known to be involved in CMT, with mainly SNVs and short indels described. Herein targeted NGS and the CovCopCan bioinformatic tool were used in two unrelated families, both presenting with typical CMT symptoms with pyramidal involvement. We have discovered two large SVs in KIF5A, a gene known to cause axonal forms of CMT (CMT2) in which no SVs have yet been described. In the first family, the patient presented with a large deletion of 12 kb in KIF5A from Chr12:57,956,278 to Chr12:57,968,335 including exons 2-15, that could lead to mutation c.(130-943_c.1717-533del), p.(Gly44_Leu572del). In the second family, two cases presented with a large deletion of 3 kb in KIF5A from Chr12:57,974,133 to Chr12:57,977,210 including exons 24-28, that could lead to mutation c.(2539-605_*36 + 211del), p.(Leu847_Ser1032delins33). In addition, bioinformatic sequence analysis revealed that a NAHR (Non-Allelic-Homologous-Recombination) mechanism, such as those in the PMP22 duplication, could be responsible for one of the KIF5A SVs and could potentially be present in a number of other patients. This study reveals that large KIF5A deletions can cause CMT2 and highlights the importance of analyzing not only the SNVs but also the SVs during diagnosis of neuropathies. |
| Databáze: | OpenAIRE |
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