Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia.

N. Elleuch, C. Depienne, A. Benomar, A. M. O. Hernandez, X. Ferrer, B. Fontaine, D. Grid, C.M.E. Tallaksen, R. Zemmouri, G. Stevanin, A. Durr, A. Brice
Neurology. 2006-03-13; 66(5): 654-659
DOI: 10.1212/01.wnl.0000201185.91110.15

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1. Neurology. 2006 Mar 14;66(5):654-9.

Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary
spastic paraplegia.

Elleuch N(1), Depienne C, Benomar A, Hernandez AM, Ferrer X, Fontaine B, Grid D,
Tallaksen CM, Zemmouri R, Stevanin G, Durr A, Brice A.

Author information:
(1)INSERM U679, Neurology and Experimental Therapeutics, Département de
Génétique, Cytogénétique, et Embryologie, Hôpital de la Pitié-Salpêtrière,
Université Pierre et Marie Curie, Faculté de Médecine, Paris, France.

BACKGROUND: Mutations in the SPG7 gene, which encodes paraplegin, are responsible
for an autosomal recessive hereditary spastic paraplegia (HSP).
OBJECTIVE: To screen the SPG7 gene in a large population of HSP families
compatible with autosomal recessive transmission.
METHODS: The authors analyzed 136 probands with pure or complex HSP for mutations
in the SPG7 using denaturation high-performance liquid chromatography and direct
RESULTS: The authors identified 47 variants including 6 mutations, 27
polymorphisms, and 14 changes with unknown effects. In one family from Morocco,
compound c.850_851delTTinsC and c.1742_1744delTGG heterozygous mutations were
shown to be causative. This family had complex HSP with cerebellar impairment.
Progression of the disease was rapid, resulting in a severe disease after 8 years
of duration. Also detected were 20 families with one heterozygous mutation that
was not found in a large control population. The mutations produced highly
defective proteins in four of these families, suggesting that they were probably
causative. Direct sequencing of all exons and reverse transcription PCR
experiments demonstrated the absence of a second mutation. However, the
p.Ala510Val missense substitution previously described as a polymorphism was
shown to be significantly associated with HSP, suggesting that it had a
functional effect.
CONCLUSION: SPG7 mutations account for less than 5% of hereditary spastic
paraplegia (HSP) families compatible with autosomal recessive inheritance.
Cerebellar signs or cerebellar atrophy on brain imaging were the most frequent
additional features in patients with SPG7 HSP. Rare nucleotide variants in SPG7
are frequent, complicating routine diagnosis.

DOI: 10.1212/01.wnl.0000201185.91110.15
PMID: 16534102 [Indexed for MEDLINE]

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