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.
| Original language | English |
|---|---|
| Pages (from-to) | 586-591 |
| Journal | Neuromuscular Disorders |
| Volume | 28 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2018 |
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Keywords
- GAA
- Gene panels
- HyperCKemia
- Late onset Pompe disease (LOPD)
- LGMD
- Metabolic myopathies
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Neurology
- Clinical Neurology
- Genetics(clinical)
Cite this
Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease. / Savarese, Marco; Torella, Annalaura; Musumeci, Olimpia; Angelini, Corrado; Astrea, Guja; Bello, Luca; Bruno, Claudio; Comi, Giacomo Pietro; Di Fruscio, Giuseppina; Piluso, Giulio; Di Iorio, Giuseppe; Ergoli, Manuela; Esposito, Gaia; Fanin, Marina; Farina, Olimpia; Fiorillo, Chiara; Garofalo, Arcomaria; Giugliano, Teresa; Magri, Francesca; Minetti, Carlo; Moggio, Maurizio; Passamano, Luigia; Pegoraro, Elena; Picillo, Ester; Sampaolo, Simone; Santorelli, Filippo Maria; Semplicini, Claudio; Udd, Bjarne; Toscano, Antonio; Politano, Luisa; Nigro, Vincenzo.
In: Neuromuscular Disorders, Vol. 28, No. 7, 2018, p. 586-591.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease
AU - Savarese, Marco
AU - Torella, Annalaura
AU - Musumeci, Olimpia
AU - Angelini, Corrado
AU - Astrea, Guja
AU - Bello, Luca
AU - Bruno, Claudio
AU - Comi, Giacomo Pietro
AU - Di Fruscio, Giuseppina
AU - Piluso, Giulio
AU - Di Iorio, Giuseppe
AU - Ergoli, Manuela
AU - Esposito, Gaia
AU - Fanin, Marina
AU - Farina, Olimpia
AU - Fiorillo, Chiara
AU - Garofalo, Arcomaria
AU - Giugliano, Teresa
AU - Magri, Francesca
AU - Minetti, Carlo
AU - Moggio, Maurizio
AU - Passamano, Luigia
AU - Pegoraro, Elena
AU - Picillo, Ester
AU - Sampaolo, Simone
AU - Santorelli, Filippo Maria
AU - Semplicini, Claudio
AU - Udd, Bjarne
AU - Toscano, Antonio
AU - Politano, Luisa
AU - Nigro, Vincenzo
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - GAA
KW - Gene panels
KW - HyperCKemia
KW - Late onset Pompe disease (LOPD)
KW - LGMD
KW - Metabolic myopathies
UR - http://www.scopus.com/inward/record.url?scp=85047872795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047872795&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2018.03.011
DO - 10.1016/j.nmd.2018.03.011
M3 - Article
AN - SCOPUS:85047872795
VL - 28
SP - 586
EP - 591
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 7
ER -