Spastic paraplegia 5: Locus refinement, candidate gene analysis and clinical description.
Am. J. Med. Genet.. 2007-05-14; 144B(7): 854-861
DOI: 10.1002/ajmg.b.30518
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1. Am J Med Genet B Neuropsychiatr Genet. 2007 Oct 5;144B(7):854-61.
Spastic paraplegia 5: Locus refinement, candidate gene analysis and clinical
description.
Klebe S(1), Durr A, Bouslam N, Grid D, Paternotte C, Depienne C, Hanein S,
Bouhouche A, Elleuch N, Azzedine H, Poea-Guyon S, Forlani S, Denis E, Charon C,
Hazan J, Brice A, Stevanin G.
Author information:
(1)INSERM U679, Pierre and Marie Curie Paris 6 University, Pitié-Salpêtrière
Hospital, 47 Boulevard de l’Hôpital, 75651 Paris Cedex 13, France.
Thirty-three different loci for hereditary spastic paraplegias (HSP) have been
mapped, and 15 responsible genes have been identified. Autosomal recessive
spastic paraplegias (ARHSPs) usually have clinically complex phenotypes but the
SPG5, SPG24, and SPG28 loci are considered to be associated with pure forms of
the disease. We performed a genome-wide scan in a large French family. Fine
mapping of the refined SPG5 region on chromosome 8q12 was performed in another 17
ARHSP families with additional microsatellite markers. After exclusion of known
ARHSP loci, the genome-wide screen provided evidence of linkage with a maximal
multipoint lod score of 2.6 in the D8S1113-D8S1699 interval. This interval
partially overlapped SPG5 and reduced it to a 5.9 megabase (Mb)-region between
D8S1113 and D8S544. In a family of Algerian origin from a series of 17 other
ARHSP kindreds, linkage to the SPG5 locus was supported by a multipoint lod score
of 2.3. The direct sequencing of the coding exons of seven candidate genes did
not detect mutations/polymorphisms in the index cases of both linked families.
The phenotype of the two SPG5-linked families consisted of spastic paraparesis
associated with deep sensory loss. In several patients with long disease
durations, there were also mild cerebellar signs. The frequency of SPG5 was
approximately 10% (2/18) in our series of ARHSP families with pure or complex
forms. We have refined the SPG5 locus to a 3.8 cM interval and extended the
phenotype of this form of ARHSP to include slight cerebellar signs.
(c) 2007 Wiley-Liss, Inc.
DOI: 10.1002/ajmg.b.30518
PMID: 17503452 [Indexed for MEDLINE]