RT Journal Article
T1 Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy.
A1 Lupo, Vincenzo
A1 García-García, Francisco
A1 Sancho, Paula
A1 Tello, Cristina
A1 García-Romero, Mar
A1 Villarreal, Liliana
A1 Alberti, Antonia
A1 Sivera, Rafael
A1 Dopazo, Joaquín
A1 Pascual-Pascual, Samuel I
A1 Márquez-Infante, Celedonio
A1 Casasnovas, Carlos
A1 Sevilla, Teresa
A1 Espinós, Carmen
AB Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (A mutation was detected in two cases; novel changes and/or variants with low frequency (A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies.
YR 2016
FD 2016-01-02
LK http://hdl.handle.net/10668/9720
UL http://hdl.handle.net/10668/9720
LA en
DS RISalud
RD Apr 12, 2025