Clinical and genetic study of a large SPG4 Italian family.
A novel SPG4 906delT frame-shift mutation in exon 6 was identified in a large Italian family with an autosomal dominant form of hereditary spastic paraplegia (ADHSP). Intrafamilial phenotypic variations observed in the pedigree included spasticity and additional clinical features, such as peripheral sensory-motor neuropathy, cognitive impairment, and urological dysfunction. Severe clinical features were found predominantly in the men who were affected, and there was no statistically significant correlation of disability and time since onset of symptoms, suggesting the existence of other genetic/nongenetic modifier(s), including gender.
Orlacchio
Antonio
A
Laboratorio di Neurogenetica, IRCCS Santa Lucia, Rome, Italy. a.orlacchio@hsantalucia.it
Kawarai
Toshitaka
T
Gaudiello
Fabrizio
F
Totaro
Antonio
A
Schillaci
Orazio
O
Stefani
Alessandro
A
Floris
Roberto
R
St George-Hyslop
Peter H
PH
Sorbi
Sandro
S
Bernardi
Giorgio
G
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000503:physiopathology; D000074181:Spastin; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human