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Narrowing of the critical region in autosomal recessive spastic paraplegia linked to the SPG5 locus
Author(s) -
Muglia M,
Criscuolo C,
Magariello A,
De Michele G,
Scarano V,
D’Adamo P,
Ambrosio G,
Gabriele AL,
Patitucci A,
Mazzei R,
Conforti FL,
Sprovieri T,
Morgante L,
Epifanio A,
La Spina P,
Valentino P,
Gasparini P,
Filla A,
Quattrone A
Publication year - 2004
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1085-9489.2004.009209bo.x
Subject(s) - hereditary spastic paraplegia , genetics , locus (genetics) , haplotype , lod score , genetic linkage , microsatellite , gene , spastic , spasticity , biology , allele , chromosome , medicine , gene mapping , phenotype , cerebral palsy , psychiatry , physical therapy
Hereditary spastic paraplegias are neurodegenerative disorders characterized clinically by progressive spasticity of the lower limbs; they are inherited as autosomal dominant, autosomal recessive and X‐linked traits. We have analyzed four autosomal recessive HSP families gathered from southern Italy. We performed genetic analysis using microsatellite markers associated with SPG5, SPG7, SPG11 and SPG14. Positive lod scores were obtained with markers located on chromosome 8. The lod scores for the four combined families were significantly higher than 3 for D8S509, D8S1102, D8S1723 and D8S260 with a maximum two‐point lod score at θ = 0 of 3.99 for the marker D8S260. In one of the examined families, the haplotype analysis suggests two key recombination events demonstrating that the gene is localized in the 11 cM region flanked by markers D8S285 and D8S544, refining the ARHSP region by approximately 22 cm. We also analyzed five candidate genes localized within the HSP region: TOX, syndecan‐binding‐protein (SDCBP), RAB2, CA8 and PENK, but we did not find disease causing mutations.