A de novo SPAST mutation leading to somatic mosaicism is associated with a later age at onset in HSP.
Neurogenetics. 2007-06-28; 8(3): 231-233
DOI: 10.1007/s10048-007-0090-4
Lire sur PubMed
1. Neurogenetics. 2007 Aug;8(3):231-3. Epub 2007 Jun 28.
A de novo SPAST mutation leading to somatic mosaicism is associated with a later
age at onset in HSP.
Depienne C, Fedirko E, Faucheux JM, Forlani S, Bricka B, Goizet C, Lesourd S,
Stevanin G, Ruberg M, Durr A, Brice A.
SPG4/SPAST, the gene-encoding spastin, is responsible for the most frequent form
of autosomal dominant hereditary spastic paraplegia (HSP). SPG4-HSP is a
heterogeneous disorder characterized by both interfamilial and intrafamilial
variation, especially regarding the severity and the age at onset. In this study,
we investigated the origin of the mutation and the factors involved in
intra-familial heterogeneity in a family with a SPG4 mutation. We demonstrated
that the mutation occurred de novo and show evidence of somatic mosaicism in the
grandfather, who was the only affected member of six siblings. His disease began
at age 55, much later than in his daughter, who had onset at age 18, and his
grandson, in whom onset was at age 5. These observations indicate that de novo
mutations can occur in SPG4, and that somatic mosaicism might account for
intra-familial variation in SPG4-linked HSP.
DOI: 10.1007/s10048-007-0090-4
PMID: 17597328 [Indexed for MEDLINE]