TY - JOUR
T1 - Diagnostic yield of multi-gene panel for muscular dystrophies and other hereditary myopathies
AU - Winckler, Pablo Brea
AU - Chwal, Bruna Cristine
AU - Dos Santos, Marco Antonnio Rocha
AU - Burguêz, Daniela
AU - Polese-Bonatto, Marcia
AU - Zanoteli, Edmar
AU - Siebert, Marina
AU - Vairo, Filippo Pinto e.
AU - Chaves, Márcia Lorena Fagundes
AU - Saute, Jonas Alex Morales
N1 - Publisher Copyright:
© 2022, Fondazione Società Italiana di Neurologia.
PY - 2022/7
Y1 - 2022/7
N2 - Genetic testing is being considered the first-step in the investigation of hereditary myopathies. However, the performance of the different testing approaches is little known. The aims of the present study were to evaluate the diagnostic yield of a next-generation sequencing panel comprising 39 genes as the first-tier test for genetic myopathies diagnosis and to characterize clinical and molecular findings of families from southern Brazil. Fifty-one consecutive index cases with clinical suspicion of genetic myopathies were recruited from October 2014 to March 2018 in a cross-sectional study. The overall diagnostic yield of the next-generation sequencing panel was 52.9%, increasing to 60.8% when including cases with candidate variants. Multi-gene panel solved the diagnosis of 12/25 (48%) probands with limb-girdle muscular dystrophies, of 7/14 (50%) with congenital muscular diseases, and of 7/10 (70%) with muscular dystrophy with prominent joint contractures. The most frequent diagnosis for limb-girdle muscular dystrophies were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related; for congenital muscular diseases, RYR1-related-disorders; and for muscular dystrophy with prominent joint contractures, Emery-Dreifuss-muscular-dystrophy-type-1 and COL6A1-related-disorders. In summary, the customized next-generation sequencing panel when applied in the initial investigation of genetic myopathies results in high diagnostic yield, likely reducing patient’s diagnostic odyssey and providing important information for genetic counseling and participation in disease-specific clinical trials.
AB - Genetic testing is being considered the first-step in the investigation of hereditary myopathies. However, the performance of the different testing approaches is little known. The aims of the present study were to evaluate the diagnostic yield of a next-generation sequencing panel comprising 39 genes as the first-tier test for genetic myopathies diagnosis and to characterize clinical and molecular findings of families from southern Brazil. Fifty-one consecutive index cases with clinical suspicion of genetic myopathies were recruited from October 2014 to March 2018 in a cross-sectional study. The overall diagnostic yield of the next-generation sequencing panel was 52.9%, increasing to 60.8% when including cases with candidate variants. Multi-gene panel solved the diagnosis of 12/25 (48%) probands with limb-girdle muscular dystrophies, of 7/14 (50%) with congenital muscular diseases, and of 7/10 (70%) with muscular dystrophy with prominent joint contractures. The most frequent diagnosis for limb-girdle muscular dystrophies were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related; for congenital muscular diseases, RYR1-related-disorders; and for muscular dystrophy with prominent joint contractures, Emery-Dreifuss-muscular-dystrophy-type-1 and COL6A1-related-disorders. In summary, the customized next-generation sequencing panel when applied in the initial investigation of genetic myopathies results in high diagnostic yield, likely reducing patient’s diagnostic odyssey and providing important information for genetic counseling and participation in disease-specific clinical trials.
KW - Diagnosis
KW - Hereditary myopathy
KW - Muscular dystrophy
KW - Next generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=85124717662&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124717662&partnerID=8YFLogxK
U2 - 10.1007/s10072-022-05934-y
DO - 10.1007/s10072-022-05934-y
M3 - Article
C2 - 35175440
AN - SCOPUS:85124717662
SN - 1590-1874
VL - 43
SP - 4473
EP - 4481
JO - Neurological Sciences
JF - Neurological Sciences
IS - 7
ER -