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Refinement of the SPG9 locus on chromosome 10q23.3‐24.2 and exclusion of candidate genes
Author(s) -
Panza E.,
Pippucci T.,
Cusano R.,
Lo Nigro C.,
Pradella L.,
Contardi S.,
Rouleau G. A.,
Stevanin G.,
Ravazzolo R.,
Liguori R.,
Montagna P.,
Romeo G.,
Seri M.
Publication year - 2008
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/j.1468-1331.2008.02117.x
Subject(s) - locus (genetics) , candidate gene , genetics , hereditary spastic paraplegia , gene , positional cloning , biology , genetic heterogeneity , disease gene identification , exome sequencing , phenotype
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 .