Publikation

Phenotypes in Swiss patients with familial ALS carrying TARDBP mutations

Wissenschaftlicher Artikel/Review - 10.01.2013

Bereiche
PubMed
DOI

Zitation
Czell D, Andersen P, Morita M, Neuwirth C, Perren F, Weber M. Phenotypes in Swiss patients with familial ALS carrying TARDBP mutations. Neurodegener Dis 2013; 12:150-5.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Neurodegener Dis 2013; 12
Veröffentlichungsdatum
10.01.2013
eISSN (Online)
1660-2862
Seiten
150-5
Kurzbeschreibung/Zielsetzung

BACKGROUND
Recently, mutations in the TARDBP gene encoding the TAR DNA-binding protein 43 (TDP-43) have been identified in some familial amyotrophic lateral sclerosis (ALS) and sporadic ALS patients. The phenotype and frequency of TARDBP mutation carriers reportedly varies greatly among European populations.

OBJECTIVE
To define the phenotypic spectrum of TARDBP mutations and their frequency in a Swiss population.

METHODS
A total of 225 patients diagnosed with ALS (182 sporadic cases, 43 familial cases) were screened for TARDBP mutations. All patients were carefully examined and interviewed for a familial predisposition. Except for 1 patient who was followed at the University of Geneva, all patients were followed at the Kantonsspital St. Gallen.

RESULTS
43 patients (19.5%) had a definite family history for ALS. A TARDBP mutation was identified in 4 of these (9.3%). Two female ALS patients carried the p.Asn352Ser mutation. Both had limb onset and a slowly progressive course of the disease. A novel mutation (p.Gly376Asp) was identified in a 44-year-old female patient. Survival amongst affected family members varied between 6 and 18 months. The patient and also the other siblings affected with ALS had an accessory nipple. A fourth male patient carried the p.Ala90Val mutation. None of the patients had overt cognitive impairment. TARDBP mutations were not found among patients with sporadic forms of ALS.

CONCLUSION
In this Swiss population, the frequency of familial ALS is higher than reported earlier in other populations. The novel p.Gly376Asp TARDBP mutation is associated with rapid disease progression and may be associated with an accessory nipple while the p.Asn352Ser mutation is associated with slow disease progression.