TY - JOUR
T1 - Autosomal dominant hereditary spastic paraplegia
T2 - DHPLC-based mutation analysis of SPG4 reveals eleven novel mutations.
AU - Patrono, Clarice
AU - Scarano, Valentina
AU - Cricchi, Federica
AU - Melone, Mariarosa A B
AU - Chiriaco, Maria
AU - Napolitano, Alessandro
AU - Malandrini, Alessandro
AU - De Michele, Giuseppe
AU - Petrozzi, Lucia
AU - Giraldi, Carlo
AU - Santoro, Lucio
AU - Servidei, Serena
AU - Casali, Carlo
AU - Filla, Alessandro
AU - Santorelli, Filippo M.
PY - 2005/5
Y1 - 2005/5
N2 - We set up a new denaturing high-performance liquid chromatography (DHPLC)-based protocol to screen patients with autosomal dominant hereditary spastic paraplegia (AD-HSP) for mutations in SPG4. Six patients had a complicated form and 49 a pure HSP phenotype. We also analyzed 19 unrelated patients presenting with an HSP phenotype (pure in 17 and complicated in two subjects) but no clear family history, as such patients may be cases of dominant inheritance with low penetrance. The overall frequency of SPG4 mutations in our study of HSP (in which prior linkage data were unavailable) was 32.4%, rising to 46.9% when only pure AD-HSP patients were considered. This figure falls well within the range reported in different populations. Rather as expected, the clinical data available for the patients did not support an easy genotype-phenotype correlation. Moreover, the clinical picture was not influenced by the length of the predicted residual gene product. As well as identifying novel variants in SPG4, this study constitutes the molecular characterization of the largest cohort of Italian AD-HSP patients studied to date. In addition, it provided an efficient, cost-effective, and reliable detection protocol for mutational screening of SPG4, which might facilitate medical genetic counseling.
AB - We set up a new denaturing high-performance liquid chromatography (DHPLC)-based protocol to screen patients with autosomal dominant hereditary spastic paraplegia (AD-HSP) for mutations in SPG4. Six patients had a complicated form and 49 a pure HSP phenotype. We also analyzed 19 unrelated patients presenting with an HSP phenotype (pure in 17 and complicated in two subjects) but no clear family history, as such patients may be cases of dominant inheritance with low penetrance. The overall frequency of SPG4 mutations in our study of HSP (in which prior linkage data were unavailable) was 32.4%, rising to 46.9% when only pure AD-HSP patients were considered. This figure falls well within the range reported in different populations. Rather as expected, the clinical data available for the patients did not support an easy genotype-phenotype correlation. Moreover, the clinical picture was not influenced by the length of the predicted residual gene product. As well as identifying novel variants in SPG4, this study constitutes the molecular characterization of the largest cohort of Italian AD-HSP patients studied to date. In addition, it provided an efficient, cost-effective, and reliable detection protocol for mutational screening of SPG4, which might facilitate medical genetic counseling.
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M3 - Article
C2 - 15841487
AN - SCOPUS:28544451984
VL - 25
SP - 506
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 5
ER -