title: White matter lesions in spastic paraplegia with mutations in SPG5/CYP7B1.
abstract: Hereditary spastic paraplegias (HSPs) are relatively frequent disorders presenting great genetic heterogeneity. The recent identification of mutations in SPG5/CYP7B1 in six autosomal recessive kindred linked to the SPG5 locus on chromosome 8q prompted us to test the relative frequency of SPG5/CYP7B1 variants in 12 families and in sporadic HSP patients by high-resolution melting screening combined with direct sequencing. We present two patients who harbored three mutations (including two novel variants) in SPG5/CYP7B1 and white matter involvement evidenced at brain MRI. In HSP patients in whom no other genes were mutated, screening of SPG5/CYP7B1 seems to have a low diagnostic yield in autosomal recessive (8%) and sporadic (<1%) cases, even in those with complicated clinical features.
authors.affiliation: IRCCS G. Gaslini Pediatric Institute and University of Genoa, Unit of Muscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Marianna
authors.initials: M
authors.lastname: Ciccolella
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D000072474:Cytochrome P450 Family 7; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*; D010375:Pedigree; D011237:Predictive Value of Tests; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D013250:Steroid Hydroxylases / Q000235:genetics*; D055815:Young Adult
chemical_list: D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human