Study finds an unexpectedly high proportion of both carriers without symptoms and HSPers unaware of their symptoms.
The clinical analysis of the 238 mutation carriers revealed a high proportion of both asymptomatic carriers (14/238) and patients unaware of symptoms (45/238), and also permitted the redefinition of this frequent form of AD-HSP.
Autosomal dominant hereditary spastic paraplegia (AD-HSP) loci have been mapped to chromosomes 14q, 2p, 15q, 8q and 12q. The SPG4 locus at 2p21-p22 has been shown to account for approximately 40% of all AD-HSP families. SPG4 encoding spastin, a putative nuclear AAA protein, has recently been identified. Here, sequence analysis of the 17 exons of SPG4 in 87 unrelated AD-HSP patients has resulted in the detection of 34 novel mutations. These SPG4 mutations are scattered along the coding region of the gene and include all types of DNA modification including missense (28%), nonsense (15%) and splice site point (26.5%) mutations as well as deletions (23%) and insertions (7.5%).
Hum Mol Genet. 2000 Mar 1;9(4):637-44.
Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia.
Fonknechten N, Mavel D, Byrne P, Davoine CS, Cruaud C, Bonsch D, Samson D, Coutinho P, Hutchinson M, McMonagle P, Burgunder JM, Tartaglione A, Heinzlef O, Feki I, Deufel T, Parfrey N, Brice A, Fontaine B, Prud’homme JF, Weissenbach J, Durr A, Hazan J.
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