Journal Article

Late-onset Pompe disease in France: molecular features and epidemiology from a nationwide study

Marie De Antonio, Piraud, M, Bedat-Millet, A L, Semplicini, Claudio, Chapon, F, Bouhour, Françoise, Eymard, B, Zagnoli, Fabien, Hogrel, J Y, Laloui, K, Froissart, Roseline, Letard, Pascaline, Journel, H, Pouget, J, Benistan, K, Laforêt, Pascal, Cintas, P, Tiffreau, V, Lagrange, E, Bassez, G, Castaing, Y, Boyer, F, Petiot, P, Feasson, L, Perniconi, Barbara, Praline, J, Solé, Guilhem, Carlier, P G, Béhin, A, Orlikowski, David, Prigent, H, Nathier, C, Caillaud, Catherine, Lacour, A, Péréon, Y, Carlier, R Y, Pellegrini, N, Juntas-Morales, R, Magy, L, Ollivier, G, Salort-Campana, Emmanuelle, Furby, A, Michaud, M, Deibener-Kaminsky, J, Germain, D, Vincent, D, Desnuelle, C, Minot-Myhié, M C, Hamroun, Dalil, Echaniz-Laguna, Andoni, Taouagh, Nadjib, Leonard-Louis, S, Bouibede, F, Durieu, I, Renard, D, Krim, E, Tard, C, Sacconi, Sabrina, Stojkovic, T, Canal, A, Nadaj-Pakleza, A, Magot, A

2018

Overview

Pompe disease (PD) is caused by a deficiency of lysosomal acid α-glucosidase resulting from mutations in the GAA gene. The clinical spectrum ranges from a rapidly fatal multisystemic disorder (classic PD, onset < 1 year) to a milder adult onset myopathy. The aims of this study were to characterize the GAA mutations, to establish the disease epidemiology, and to identify potential genotype-phenotype correlations in French late-onset PD patients (onset ≥ 2 years) diagnosed since the 1970s. Data were collected from the two main laboratories involved in PD diagnosis and from the French Pompe registry. Two hundred forty-six patients (130 females and 116 males) were included, with a mean age at diagnosis of 43 years. Eighty-three different mutations were identified in the GAA gene, among which 28 were novel. These variants were spread all over the sequence and included 42 missense (one affecting start codon), 8 nonsense, 15 frameshift, 14 splice mutations, 3 small in-frame deletions, and one large deletion. The common c.-32-13T>G mutation was detected in 151/170 index cases. Other frequent mutations included the exon 18 deletion, the c.525del, and the missense mutations c.1927G>A (p.Gly643Arg) and c.655G>A (p.Gly219Arg). Patients carrying the c.-32-13T>G mutation had an older mean age at onset than patients non-exhibiting this mutation (36 versus 25 years). Patients with the same genotype had a highly variable age at onset. We estimated the frequency of late-onset PD in France around 1/69,927 newborns. In conclusion, we characterized the French cohort of late-onset PD patients through a nationwide study covering more than 40 years.

• Publisher: Blackwell Publishing Ltd
• Subject: Diagnosis / Epidemiology / Frameshift mutation / Gene deletion / Genotypes / Missense mutation / Mutation / Myopathy / Neonates / Phenotypes / α-Glucosidase