Diagnostic yield of multi-gene panel for muscular dystrophies and other hereditary myopathies

被引:3
作者
Winckler, Pablo Brea [1 ,2 ]
Chwal, Bruna Cristine [3 ]
Rocha Dos Santos, Marco Antonnio [1 ,2 ]
Burguez, Daniela [3 ]
Polese-Bonatto, Marcia [3 ]
Zanoteli, Edmar [4 ]
Siebert, Marina [5 ,6 ,7 ]
Pinto e Vairo, Filippo [8 ,9 ]
Fagundes Chaves, Marcia Lorena [1 ,2 ,10 ]
Morales Saute, Jonas Alex [1 ,2 ,3 ,10 ]
机构
[1] Univ Fed Rio Grande Sul UFRGS, Grad Program Med Med Sci, Porto Alegre, RS, Brazil
[2] Hosp Clin Porto Alegre HCPA, Neurol Div, Porto Alegre, RS, Brazil
[3] HCPA, Med Genet Div, Ramiro Barcelos 2350, BR-90035903 Porto Alegre, RS, Brazil
[4] Univ Sao Paulo, Fac Med, Dept Neurol, Sao Paulo, Brazil
[5] Univ Fed Rio Grande Sul UFRGS, Grad Program Sci Gastroenterol & Hepatol, Porto Alegre, RS, Brazil
[6] Hosp Clin Porto Alegre HCPA, Expt Res Ctr, Unit Lab Res, Porto Alegre, RS, Brazil
[7] Hosp Clin Porto Alegre HCPA, Expt Res Ctr, BRAIN Basic Res & Adv Invest Neurosci Lab, Porto Alegre, RS, Brazil
[8] Mayo Clin, Ctr Individualized Med, Rochester, MN USA
[9] Mayo Clin, Dept Clin Genom, Rochester, MN USA
[10] Univ Fed Rio Grande do Sul, Dept Internal Med, Porto Alegre, RS, Brazil
关键词
Diagnosis; Next generation sequencing; Muscular dystrophy; Hereditary myopathy; CLINICAL-FEATURES; PREVALENCE; VARIANTS; GENOMICS;
D O I
10.1007/s10072-022-05934-y
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:4473 / 4481
页数:9
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