Title :

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

Author(s) :

Semplicini, Claudio [Auteur]
Letard, Pascaline [Auteur]
De Antonio, Marie [Auteur]
Taouagh, Nadjib [Auteur]
Perniconi, Barbara [Auteur]
Bouhour, Françoise [Auteur]
Echaniz-Laguna, Andoni [Auteur]
Orlikowski, David [Auteur]
Sacconi, Sabrina [Auteur]
Salort-Campana, Emmanuelle [Auteur]
Solé, Guilhem [Auteur]
Zagnoli, Fabien [Auteur]
Hamroun, Dalil [Auteur]
Froissart, Roseline [Auteur]
Caillaud, Catherine [Auteur]
Laforêt, Pascal [Auteur]

Journal title :

Journal of inherited metabolic disease

Abbreviated title :

J. Inherit. Metab. Dis.

Publication date :

2018-08-28

ISSN :

1573-2665

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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) ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Collections :

• Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - EA 7369

Research team(s) :

Activité Physique, Muscle, Santé (APMS)

Submission date :

2019-09-24T10:01:49Z