Dystroglycanopathy (α-DG) is a relatively common, clinically and genetically heterogeneous category of congenital forms of muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) associated with hypoglycosylated α-dystroglycan. To date, mutations in at least 19 genes have been associated with α-DG. One of them, GMPPB, encoding the guanosine-diphosphate-mannose (GDP-mannose) pyrophosphorylase B protein, has recently been associated with a wide clinical spectrum ranging from severe Walker-Warburg syndrome to pseudo-metabolic myopathy and even congenital myasthenic syndromes. We re-sequenced the full set of known disease genes in 73 Italian patients with evidence of either reduced or nearly absent α-dystroglycan to assess genotype-phenotype correlations in this cohort. We used innovative bioinformatic tools to calculate the effects of all described GMPPB mutations on protein function and attempted to correlate them with phenotypic expressions.
Broad phenotypic spectrum and genotype-phenotype correlations in GMPPB-related dystroglycanopathies: An Italian cross-sectional study / Astrea, G.; Romano, A.; Angelini, C.; Antozzi, C. G.; Barresi, R.; Battini, R.; Battisti, C.; Bertini, E.; Bruno, C.; Cassandrini, D.; Fanin, M.; Fattori, F.; Fiorillo, C.; Guerrini, R.; Maggi, L.; Mercuri, E.; Morani, F.; Mora, M.; Moro, F.; Pezzini, I.; Picillo, E.; Pinelli, M.; Politano, L.; Rubegni, A.; Sanseverino, W.; Savarese, M.; Striano, P.; Torella, A.; Trevisan, C. P.; Trovato, R.; Zaraieva, I.; Muntoni, F.; Nigro, V.; D'Amico, A.; Santorelli, F. M.; Berardinelli, A.; Comi, G.; Donati, M. A.; Dotti, M. T.; Grandis, M.; Magri, F.; Maioli, M. A.; Malandrini, A.; Mari, F.; Massa, R.; Merlini, L.; Moggio, M.; Morandi, L. O.; Musumeci, O.; Pane, M.; Pini, A.; Pegoraro, E.; Pennisi, E. M.; Peverelli, L.; Ricci, G.; Rodolico, C.; Ruggiero, L.; Sacchini, M.; Santoro, Lucio.; Siciliano, G.; Simonati, A.; Tonin, P.; Toscano, A.. - In: ORPHANET JOURNAL OF RARE DISEASES. - ISSN 1750-1172. - 13:1(2018), p. 170. [10.1186/s13023-018-0863-x]
Broad phenotypic spectrum and genotype-phenotype correlations in GMPPB-related dystroglycanopathies: An Italian cross-sectional study
Pinelli M.;Santorelli F. M.;Ruggiero L.;Santoro Lucio.;
2018
Abstract
Dystroglycanopathy (α-DG) is a relatively common, clinically and genetically heterogeneous category of congenital forms of muscular dystrophy (CMD) and limb-girdle muscular dystrophy (LGMD) associated with hypoglycosylated α-dystroglycan. To date, mutations in at least 19 genes have been associated with α-DG. One of them, GMPPB, encoding the guanosine-diphosphate-mannose (GDP-mannose) pyrophosphorylase B protein, has recently been associated with a wide clinical spectrum ranging from severe Walker-Warburg syndrome to pseudo-metabolic myopathy and even congenital myasthenic syndromes. We re-sequenced the full set of known disease genes in 73 Italian patients with evidence of either reduced or nearly absent α-dystroglycan to assess genotype-phenotype correlations in this cohort. We used innovative bioinformatic tools to calculate the effects of all described GMPPB mutations on protein function and attempted to correlate them with phenotypic expressions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
