Refinement of the SPG9 locus on chromosome 10q23.3-24.2 and exclusion of candidate genes.
Eur J Neurol. 2008-05-01; 15(5): 520-524
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1. Eur J Neurol. 2008 May;15(5):520-4. doi: 10.1111/j.1468-1331.2008.02117.x.
Refinement of the SPG9 locus on chromosome 10q23.3-24.2 and exclusion of
Panza E(1), Pippucci T, Cusano R, Lo Nigro C, Pradella L, Contardi S, Rouleau GA,
Stevanin G, Ravazzolo R, Liguori R, Montagna P, Romeo G, Seri M.
(1)Laboratory of Medical Genetics, Department of Internal Medicine,
Cardioangiology and Hepatology, University of Bologna, Bologna, Italy.
BACKGROUND AND PURPOSE: The hereditary spastic paraplegias (HSPs) are a
heterogeneous group of neurodegenerative disorders, characterized by a
progressive spasticity of the lower limbs. So far, 33 different loci (SPGs) have
been mapped and the 15 genes responsible have been identified. We mapped a locus
responsible for a form of spastic paraplegia, complicated by bilateral cataracts,
gastroesophageal reflux with persisting vomiting and amyotrophy to chromosome
10q23.3-q24.2, in an Italian family. The critical region was in a 12 cm
chromosomal interval between markers D10S564 and D10S603 (SPG9, MIM601162). In
the same region, two other forms of HSP have been recently mapped: SPG27 and
SPG33. In the latter case, the gene responsible has been identified.
MATERIALS AND METHODS: To better characterize this region, we genotyped
individuals from SPG9-linked families using additional markers and reduced the
candidate region to a 4.8 Mb, excluding several genes by positional cloning.
RESULTS: The refined SPG9 locus is positioned completely within SPG27 and does
not include the SPG33 gene.
DISCUSSION: Fifty-two transcripts are present in the refined critical region and
25 strong candidates have been excluded as disease causing genes by direct
sequencing. Six of them were also excluded as responsible for SPG27.
PMID: 18394049 [Indexed for MEDLINE]