[show abstract][hide abstract] ABSTRACT: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive neurodegenerative disease, recently associated with mutations in the aprataxin gene. Main features are early onset cerebellar ataxia, oculomotor apraxia and peripheral neuropathy. The presence of choreoathetosis or dystonia in some patients suggests basal ganglia involvement, but these structures appear preserved in a single case in which neuropathological examination was performed. To evaluate in vivo the nigrostriatal function we studied dopamine transporter (DAT) density with [(123)I] 2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT)-SPECT in four AOA1 patients and eight healthy volunteers. All patients showed ataxia and neuropathy; only one had chorea and none had dystonia. Comparing with controls, AOA1 patients showed a slight reduction of the average striatal DAT density, which was bilateral and uniform in caudate and putamen. Nigrostriatal impairment occurred even in the absence of extrapyramidal features. Our data suggest subclinical involvement of basal ganglia in AOA1.
Journal of Neurology 02/2008; 255(1):45-8. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal-recessive disorder caused by mutations in the PANK2 gene. The authors report clinical and genetic findings of 16 patients with PKAN. The authors identified 12 mutations in the PANK2 gene, five of which were new. Only nine patients could be classified as classic or atypical PKAN, and intermediate phenotypes are described. Two patients presented with motor tics and obsessive-compulsive behavior suggestive of Tourette syndrome.
[show abstract][hide abstract] ABSTRACT: Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive disorder characterized by early-onset cerebellar ataxia, oculomotor apraxia, and peripheral neuropathy. The causative gene (APTX) has been recently identified in Portuguese and Japanese kindreds. Three patients with AOA1 were identified in an APTX mutation screening on 28 Southern Italian patients with progressive ataxia and peripheral neuropathy. A novel homozygous missense mutation (H201Q) was found in one patient and a Japanese missense mutation (P206L) in two. AOA1 clinical heterogeneity and onset later than previously described are shown.
[show abstract][hide abstract] ABSTRACT: 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. Four Italian families with autosomal recessive pure spastic paraplegia are reported. We show evidence of linkage to the SPG5 locus on chromosome 8p and our data reduce the candidate interval for SPG5 to the11-cM interval spanned by D8S285 and D8S544. We also report the search for mutations in five genes located in the region and their exclusion as candidates for SPG5.
[show abstract][hide abstract] ABSTRACT: A complicated form of recessive hereditary spastic paraplegias (HSPs) with thin corpus callosum (TCC) was first described in Japan, and most of the Japanese families showed linkage to chromosome 15q13-15. A recessive HSP locus (SPG11) has also been mapped to chromosome 15q13-15 in Italian and North American families with and without TCC, and it overlaps the region identified in the Japanese families.
To study clinically and genetically 12 Italian families with HSP and TCC.
The authors investigated 18 affected and 30 healthy individuals from 12 unrelated Italian families with recessive HSP-TCC. Clinical, neurophysiologic, and neuroradiologic studies were undertaken. All patients were negative for SPG7 mutations. Genetic linkage analyses were carried out with polymorphic DNA markers on 15q13-15.
Five families were consistent with linkage, thus defining a 19.8-cM region between markers D15S1007 and D15S978, encompassing the SPG11 interval. In one consanguineous family, linkage could be firmly excluded, confirming genetic heterogeneity. Two families appeared not linked to the region, but this could not be firmly proved because of the small family size. The remaining four families were uninformative for linkage purposes.
HSP-TCC is common in Italy. The phenotype is fairly homogeneous and is associated with impaired cognition. There are at least two loci for HSP-TCC, one of which is on chromosome 15q13-15.
[show abstract][hide abstract] ABSTRACT: A form of autosomal recessive spastic ataxia (ARSACS) has been described in the Charlevoix and Saguenay regions of Quebec. So far a frameshift and a nonsense mutation have been identified in the SACS gene. The authors report a new mutation (1859insC), leading to a frameshift with a premature termination of the gene product sacsin, in two sisters from consanguineous parents. The phenotype is similar to previously described patients with ARSACS.
[show abstract][hide abstract] ABSTRACT: The accuracy of the diagnostic criteria for Friedreich's ataxia proposed by Harding and by the Quebec Cooperative Study on Friedreich's Ataxia was studied in 142 patients with progressive unremitting ataxia of autosomal recessive inheritance or sporadic occurrence. Eighty-eight patients received the molecular diagnosis of Friedreich's ataxia. Traditional diagnostic criteria are characterized by high specificity, but they yield a high number of false-negative diagnoses. We suggest three levels of diagnostic certainty: (1) possible Friedreich's ataxia, defined as sporadic or recessive progressive ataxia with (a) lower limb areflexia and dysarthria, Babinski sign, or electrocardiographic repolarization abnormalities, or (b) with lower limb retained reflexes and electrocardiographic repolarization abnormalities (95% sensitivity and 88% positive predictive value); (2) probable Friedreich's ataxia as defined by Harding's criteria (63% sensitivity and 96% positive predictive value) or by Quebec Cooperative Study on Friedreich's Ataxia criteria (63% sensitivity and 98% positive predictive value); (3) definite diagnosis, molecularly confirmed.
Movement Disorders 12/2000; 15(6):1255-8. · 4.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: We studied the factors that might influence onset age in Friedreich's ataxia in 41 cases (20 male, 21 female) homozygous for GAA expansion on the first intron of X25 gene. Patients came from 18 multiplex families (13 couples, 5 triplets). Mean age (SD) was 18.1 (8.9) years and did not differ by gender. Onset age and the sizes of the smaller (GAA1) and the larger (GAA2) allele in each pair showed high intrafamily correlation. We found an inverse correlation between age at onset and GAA1 size, but not between age at onset and GAA2 size. Stepwise multiple regression of onset age on GAA1 size, sibling onset age, and GAA2 size showed that GAA1 accounts for 73% of onset age variance, and sibling onset age for an additional 13%. The study demonstrates that, in addition to GAA expansion size, other environmental or genetic familial factors influence disease expression.
Journal of Neurology 03/1998; 245(3):166-8. · 3.58 Impact Factor