Premium
The odyssey of complex neurogenetic disorders: From undetermined to positive
Author(s) -
Salinas Valeria,
Vega Patricia,
Marsili Luca,
PérezMaturo Josefina,
Martínez Nerina,
Zavala Lucia,
GonzálezMorón Dolores,
Medincy,
RodriguezQuiroga Sergio A.,
Amartino Hernán,
Maxit Clarisa,
Sturchio Andrea,
Grimberg Barbara,
Duque Kevin,
Comas Betiana,
Silva Walter,
Consalvo Damián,
Sfaello Ignacio,
Espay Alberto J.,
Kauffman Marcelo A.
Publication year - 2020
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31848
Subject(s) - exome sequencing , genetics , clinical significance , germline , biology , disease , pathogenicity , genetic heterogeneity , medical genetics , dna sequencing , gene , phenotype , bioinformatics , medicine , pathology , microbiology and biotechnology
The genetic and phenotypic heterogeneity of neurogenetic diseases forces patients and their families into a “diagnostic odyssey.” An increase in the variability of genetic disorders and the corresponding gene‐disease associations suggest the need to periodically re‐evaluate the significance of variants of undetermined pathogenicity. Here, we report the diagnostic and clinical utility of Targeted Gene Panel Sequencing (TGPS) and Whole Exome Sequencing (WES) in 341 patients with suspected neurogenetic disorders from centers in Buenos Aires and Cincinnati over the last 4 years, focusing on the usefulness of reinterpreting variants previously classified as of uncertain significance. After a mean of ±2years (IC 95:0.73–3.27), approximately 30% of the variants of uncertain significance were reclassified as pathogenic. The use of next generation sequencing methods has facilitated the identification of both germline and mosaic pathogenic variants, expanding the diagnostic yield. These results demonstrate the high clinical impact of periodic reanalysis of undetermined variants in clinical neurology.