BACKGROUND: Neuromuscular disorders are a phenotypically and genotypically diverse group of diseases that can be difficult to diagnose accurately because of overlapping clinical features and nonspecific muscle pathology. Next-generation sequencing (NGS) is a high-throughput technology that can be used as a more time- and cost-effective tool for identifying molecular diagnoses for complex genetic conditions, such as neuromuscular disorders. METHODS: One hundred and sixty-nine patients referred to a Canadian neuromuscular clinic for evaluation of possible muscle disease were screened with an NGS panel of muscular dystrophy-associated genes. Patients were categorized by the reason of referral (1) muscle weakness (n=135), (2) recurrent episodes of rhabdomyolysis (n=18), or (3) idiopathic hyperCKemia (n=16). RESULTS: Pathogenic and likely pathogenic variants were identified in 36.09% of patients (61/169). The detection rate was 37.04% (50/135) in patients with muscle weakness, 33.33% (6/18) with rhabdomyolysis, and 31.25% (5/16) in those with idiopathic hyperCKemia. CONCLUSIONS: This study shows that NGS can be a useful tool in the molecular workup of patients seen in a neuromuscular clinic. Evaluating the utility of large panels of a muscle disease-specific NGS panel to investigate the genetic susceptibilities of rhabdomyolysis and/or idiopathic hyperCKemia is a relatively new field. Twenty-eight of the pathogenic and likely pathogenic variants reported here are novel and have not previously been associated with disease.
BACKGROUND:Neuromuscular disorders are a phenotypically and genotypically diverse group of diseases that can be difficult to diagnose accurately because of overlapping clinical features and nonspecific muscle pathology. Next-generation sequencing (NGS) is a high-throughput technology that can be used as a more time- and cost-effective tool for identifying molecular diagnoses for complex genetic conditions, such as neuromuscular disorders. METHODS: One hundred and sixty-nine patients referred to a Canadian neuromuscular clinic for evaluation of possible muscle disease were screened with an NGS panel of muscular dystrophy-associated genes. Patients were categorized by the reason of referral (1) muscle weakness (n=135), (2) recurrent episodes of rhabdomyolysis (n=18), or (3) idiopathic hyperCKemia (n=16). RESULTS: Pathogenic and likely pathogenic variants were identified in 36.09% of patients (61/169). The detection rate was 37.04% (50/135) in patients with muscle weakness, 33.33% (6/18) with rhabdomyolysis, and 31.25% (5/16) in those with idiopathic hyperCKemia. CONCLUSIONS: This study shows that NGS can be a useful tool in the molecular workup of patients seen in a neuromuscular clinic. Evaluating the utility of large panels of a muscle disease-specific NGS panel to investigate the genetic susceptibilities of rhabdomyolysis and/or idiopathic hyperCKemia is a relatively new field. Twenty-eight of the pathogenic and likely pathogenic variants reported here are novel and have not previously been associated with disease.
Entities:
Keywords:
congenital myopathy; hyperCKemia; muscular dystrophy; next generation sequencing; rhabdomyolysis
Authors: Osorio Lopes Abath Neto; Livija Medne; Sandra Donkervoort; Maria Elena Rodríguez-García; Véronique Bolduc; Ying Hu; Eleonora Guadagnin; A Reghan Foley; John F Brandsema; Allan M Glanzman; Gihan I Tennekoon; Mariarita Santi; Justin H Berger; Lynn A Megeney; Hirofumi Komaki; Michio Inoue; Francisco Javier Cotrina-Vinagre; Aurelio Hernández-Lain; Elena Martin-Hernández; Linford Williams; Sabine Borell; David Schorling; Kimberly Lin; Konstantinos Kolokotronis; Uta Lichter-Konecki; Janbernd Kirschner; Ichizo Nishino; Brenda Banwell; Francisco Martínez-Azorín; Patrick G Burgon; Carsten G Bönnemann Journal: Brain Date: 2021-10-22 Impact factor: 15.255