Search results for "Trinucleotide repeat"
showing 10 items of 46 documents
GAA trinucleotide repeat expansion in variant Friedreich's ataxia families.
1997
Phenotypic variants in Friedreich's ataxia include late onset, preservation of the lower limbs tendon reflexes, and slow progression. We describe clinical and electrophysiological features from three families with Friedreichlike phenotypes. Friedreich's ataxia diagnosis was confirmed by finding two allelic expansions of the GAA trinucleotide repeat at the X25 gene. In family 1 both patients had a late-onset phenotype with preservation of knee and ankle jerks, lack of cardiomyopathy, and preserved H reflex. One of them did not have electrophysiologic evidence of sensory axonal neuropathy. Patients from family 2 showed variability in the age of onset, and 2 out of 3 affected children had hype…
Central motor conduction time by magnetic stimulation of the cortex and peripheral nerve conduction follow-up studies in Friedreich's ataxia.
1998
A follow-up clinical study, peripheral motor and sensory nerve conduction velocities and central motor conduction by magnetic stimulation of the cortex were performed in 13 patients with classical Friedreich's ataxia (FA) phenotype, for a period of 9-12 years. Clinical worsening was unrelated to peripheral nerve abnormalities. The amplitude of the nerve action potentials and delayed conduction velocity remained unchanged for several years. Central motor conduction times were abnormal in all patients. Clinical conditions worsened significantly between successive examinations with significant increments in threshold and significant decrement of the amplitude of motor evoked potentials. The re…
Hypo-excitability of cortical areas in patients affected by Friedreich ataxia: A TMS study
2005
The aim of the study was to explore excitability of a motor and a non-motor (visual) area in patients affected by Friedreich ataxia and to correlate neurophysiological data with clinical parameters. Seven patients (3M/4F) and ten healthy controls (5M/5F) participated in the study. The hot-spot for activation of right abductor pollicis brevis was checked by means of a figure-of-eight coil and the motor threshold (MT) on this point was recorded. The phosphene threshold (PT) was measured by means of a focal coil over the occipital cortex as the lower intensity of magnetic stimulation able to induce the perception of phosphenes. The patients showed a significantly higher mean PT (p<.03) and MT …
Phenotype Correlation and Intergenerational Dynamics of the Friedreich Ataxia GAA Trinucleotide Repeat
1997
Summary The Friedreich ataxia (FA) mutation has recently been identified as an unstable trinucleotide GAA repeat present 7–22 times in the normal population but amplified as many as > 1, 000 times in FA. Since it is an autosomal recessive disease, FA does not show typical features observed in other dynamic mutation disorders, such as genetic anticipation. We have analyzed the GAA repeat in 104 FA patients and 163 carrier relatives previously defined by linkage analysis. The GAA expansion was detected in all patients, most (94%) of them being ho-mozygous for the mutation. We have demonstrated that clinical variability in FA is related to the size of the expanded alleles: milder forms of the …
Muscleblind isoforms are functionally distinct and regulate α-actinin splicing
2007
Drosophila Muscleblind (Mbl) proteins control terminal muscle and neural differentiation, but their molecular function has not been experimentally addressed. Such an analysis is relevant as the human Muscleblind-like homologs (MBNL1-3) are implicated in the pathogenesis of the inherited muscular developmental and degenerative disease myotonic dystrophy. The Drosophila muscleblind gene expresses four protein coding splice forms (mblA to mblD) that are differentially expressed during the Drosophila life cycle, and which vary markedly in their ability to rescue the embryonic lethal phenotype of muscleblind mutant flies. Analysis of muscleblind mutant embryos reveals misregulated alternative sp…
Evidence for a common origin of most Friedreich ataxia chromosomes in the Spanish population
1996
Haplotype analysis is a powerful approach to understand the spectrum of mutations accounting for a disease in a homogeneous population. We show that haplotype variation for 10 markers linked to the Friedreich ataxia locus (FRDA) argues in favor of an important mutation homogeneity in the Spanish population, and positions the FRDA locus in the region where it has been recently isolated. We also report the finding of a new single nucleotide polymorphism called FAD1. The new marker shows a very strong linkage disequilibrium with Friedreich ataxia (FA) in both the Spanish and French populations. suggesting the existence of an ancient and widespread FRDA mutations. Inclusion of FAD1 in the exten…
Isolation and characterization of 10 highly polymorphic di- and trinucleotide microsatellite markers in the mayfly Ameletus inopinatus (Ephemeroptera…
2008
We describe the isolation of ten polymorphic microsatellite loci from the mayfly Ameletus inopinatus. Loci had di- or trinucleotide repeat motifs and were highly variable with three to 17 alleles (mean = 7.15). Observed heterozygosity ranged from 0.143 to 0.905. One locus (Ami_202) showed significant deviation from Hardy–Weinberg equilibrium in one population, but no evidence for null alleles. One locus (Ami_73) was significantly linked with three other loci. The remaining nine loci should prove highly informative for population genetic studies.
ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion
2015
Abstract There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS ca…
Inheritance patterns of ATCCT repeat interruptions in spinocerebellar ataxia type 10 (SCA10) expansions
2017
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta- and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats. To examine the apparent contradiction of unstable, interruption-positive SCA10 e…
Differential expression of PGC-1α and metabolic sensors suggest age-dependent induction of mitochondrial biogenesis in Friedreich ataxia fibroblasts.
2011
11 pages, 6 figures. PMID:21687738[PubMed] PMCID: PMC3110204