Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease
Articolo
Data di Pubblicazione:
2018
Citazione:
Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease / M. Savarese, A. Torella, O. Musumeci, C. Angelini, G. Astrea, L. Bello, C. Bruno, G.P. Comi, G. Di Fruscio, G. Piluso, G. Di Iorio, M. Ergoli, G. Esposito, M. Fanin, O. Farina, C. Fiorillo, A. Garofalo, T. Giugliano, F. Magri, C. Minetti, M. Moggio, L. Passamano, E. Pegoraro, E. Picillo, S. Sampaolo, F.M. Santorelli, C. Semplicini, B. Udd, A. Toscano, L. Politano, V. Nigro. - In: NEUROMUSCULAR DISORDERS. - ISSN 0960-8966. - 28:7(2018 Jul), pp. 586-591. [10.1016/j.nmd.2018.03.011]
Abstract:
Mutations in the GAA gene may cause a late onset Pompe disease presenting with proximal weakness without the characteristic muscle pathology, and therefore a test for GAA activity is the first tier analysis in all undiagnosed patients with hyperCKemia and/or limb-girdle muscular weakness. By using MotorPlex, a targeted gene panel for next generation sequencing, we analyzed GAA and other muscle disease-genes in a large cohort of undiagnosed patients with suspected inherited skeletal muscle disorders (n = 504). In this cohort, 275 patients presented with limb-girdle phenotype and/or an isolated hyperCKemia. Mutational analysis identified GAA mutations in ten patients. Further seven affected relatives were identified by segregation studies. All the patients carried the common GAA mutation c.-32-13T >G and a second, previously reported mutation. In the subcohort of 275 patients with proximal muscle weakness and/or hyperCKemia, we identified late-onset Pompe disease in 10 patients. The clinical overlap between Pompe disease and LGMDs or other skeletal muscle disorders suggests that GAA and the genes causing a metabolic myopathy should be analyzed in all the gene panels used for testing neuromuscular patients. However, enzymatic tests are essential for the interpretation and validation of genetic results.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
GAA; Gene panels; HyperCKemia; Late onset Pompe disease (LOPD); LGMD; Metabolic myopathies; Pediatrics, Perinatology and Child Health; Neurology; Neurology (clinical); Genetics (clinical)
Elenco autori:
M. Savarese, A. Torella, O. Musumeci, C. Angelini, G. Astrea, L. Bello, C. Bruno, G.P. Comi, G. Di Fruscio, G. Piluso, G. Di Iorio, M. Ergoli, G. Esposito, M. Fanin, O. Farina, C. Fiorillo, A. Garofalo, T. Giugliano, F. Magri, C. Minetti, M. Moggio, L. Passamano, E. Pegoraro, E. Picillo, S. Sampaolo, F.M. Santorelli, C. Semplicini, B. Udd, A. Toscano, L. Politano, V. Nigro
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