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.

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]

Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease

G.P. Comi;F. Magri;
2018-07

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.
GAA; Gene panels; HyperCKemia; Late onset Pompe disease (LOPD); LGMD; Metabolic myopathies; Pediatrics, Perinatology and Child Health; Neurology; Neurology (clinical); Genetics (clinical)
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/619953
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