New structural variations responsible for Charcot-Marie-Tooth disease: The first two large KIF5A deletions detected by CovCopCan software - Maintenance myélinique et neuropathies périphériques Access content directly
Journal Articles Computational and Structural Biotechnology Journal Year : 2021

New structural variations responsible for Charcot-Marie-Tooth disease: The first two large KIF5A deletions detected by CovCopCan software

Paco Derouault
Guilhem Sole

Abstract

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.
Fichier principal
Vignette du fichier
S2001037021003275.pdf (1.14 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-03402586 , version 1 (22-08-2023)

Licence

Attribution - NonCommercial

Identifiers

Cite

Ioanna Pyromali, Alexandre Perani, Angélique Nizou, Nesrine Benslimane, Paco Derouault, et al.. New structural variations responsible for Charcot-Marie-Tooth disease: The first two large KIF5A deletions detected by CovCopCan software. Computational and Structural Biotechnology Journal, 2021, 19, pp.4265-4272. ⟨10.1016/j.csbj.2021.07.037⟩. ⟨hal-03402586⟩
43 View
9 Download

Altmetric

Share

Gmail Facebook X LinkedIn More