ABSTRACT
BACKGROUND: A scale for the Assessment and Rating of Ataxia (SARA) was developed for evaluation of autosomal dominant cerebellar ataxias (ADCA) and was also recommended for clinical trials of Friedreich's ataxia patients (FRDA). FRDA, unlike ADCA, is characterized as being a sensory type of ataxia for which the disease-specific Friedreich ataxia rating scale (FARS) was developed. The objective of this study was to determine whether SARA and FARS scores are associated with posturographic parameters in FRDA patients. METHOD: Adult patients with genetically confirmed FRDA (n=11) and ADCA (n=13) were evaluated by SARA, FARS and posturography. RESULTS: FRDA patients' postural stability parameters, in stance with visual control, correlated with balance impairment in FARS (r=0.622; p<0.05) and SARA (r=0.735; p<0.05). Without visual control, only FARS correlated with balance impairment (r=0.732; p<0.05). CONCLUSION: The SARA, in FRDA patients, correlates with stance with visual control but not without visual control which emphasizes sensory ataxia. This suggests that application of the SARA in Friedreich's ataxia patients according to posturography is possible but presumably limited and FARS, although being a more time consuming scale, may have advantages over SARA in FRDA patients.
Subject(s)
Friedreich Ataxia/diagnosis , Friedreich Ataxia/physiopathology , Postural Balance/physiology , Posture/physiology , Severity of Illness Index , Adolescent , Adult , Ataxins , Child , Female , Friedreich Ataxia/genetics , Humans , Male , Middle Aged , Nerve Tissue Proteins/genetics , Statistics, Nonparametric , Young AdultABSTRACT
Expansion of CAG trinucleotide repeats has been shown to cause a number of autosomal dominant spinocerebellar ataxias such as SCA1, SCA2, SCA3/MJD, SCA6 and SCA7. These disorders are characterized by a wide inter- and intrafamiliar variation in clinical features. The same mutation can result in different phenotypes and the very similar phenotypes can be caused by different mutations. Therefore it is necessary to investigate more SCA genes (according to prevalence) to identify the causal elongation. We developed a fast and efficient screening method based on touchdown multiplex PCR with fluorescent labelled primers for the most common types of SCAs (SCA 1, 2, 3 and 7). It has been reliable in 113 probands tested. Fragment analysis was performed by using 6% denaturing polyacrylamide gel and employing the automated DNA sequencer. This method considerably shortens the process of molecular genetic screening of SCAs and might be used as a tip for designing other SCA screening sets.
Subject(s)
Polymerase Chain Reaction , Spinocerebellar Ataxias/genetics , Trinucleotide Repeat Expansion/genetics , Genetic Testing/methods , Humans , Polymerase Chain Reaction/methodsABSTRACT
BACKGROUND: Many observations indicate that genetic factors play an important role in the aetiology of autism. Up to now, however, no genetic markers have been convincingly identified which influence the predisposition to this disorder. Complex genetic analysis of autistic patients and their families may therefore lead to the identification of features which could help to direct further search for the predisposing genes. METHODS AND RESULTS: We have analysed a sample of 20 patients with autism spectrum disorders. The patients have been subjected to clinical genetic examination, cytogenetic analysis and DNA analysis of the FMR1 gene. In the sample studied we have observed more boys (15/20), various degree of mental retardation (18/20), high frequency of complications during pregnancy (10/20) and delivery (10/20), increased incidence of psychiatric disorders, behavioural abnormalities and suicides among the relatives, and increased head circumference and unusually formed ears in the probands. Three patients had different chromosomal aberrations or variants (t(21;22), inv(9) and inv(10)). One patient harboured expansion of the trinucleotide repeat sequence in the FMR1 gene on the full mutation level which is characteristic for the fragile X syndrome, and one patient is suspected to suffer from the Rett syndrome. CONCLUSIONS: Our observations confirm and extend the results reported in the literature. Most interesting are mainly the macrocephaly which may be associated with the recently described increased neonatal levels of neural growth factors in autistic individuals, ear malformations which may indicate aberrations in the HOXA1 gene pathway, the occurrence of chromosomal inversions recurrent in autism, and peculiarities in the pedigrees of the patients.
Subject(s)
Autistic Disorder/genetics , RNA-Binding Proteins , Adolescent , Adult , Child , Child, Preschool , Cytogenetic Analysis , Female , Fragile X Mental Retardation Protein , Genetic Predisposition to Disease/genetics , Humans , Male , Nerve Tissue Proteins/genetics , Pedigree , Trinucleotide RepeatsABSTRACT
BACKGROUND: Fragile X syndrome is gonosomal recessive mental retardation with the frequency 1:1000 in male population. Fragile X syndrome is caused by amplification of CGG repeat in 1. exon of FMT-1 gene. The aim of this study was to set up and validate a rapid and efficient PCR diagnosis to select FRAXA negative patients in population of mental retarded patients. METHODS AND RESULTS: In the set up phase of the method, 196 patients were diagnosed. We were using modified radioactive PCR of CGG. Obtained PCR fragments were separated on 6% denaturing PAGE. Results were correlated with Southern blot analysis using pE5.1 probe. STR-PCR was verified on a large set of patients and shows validity and efficiency of results in the case of pre- and full mutations in male hemizygous patients too. For estimation of carriers with pre- and full mutation by females modified diagnostic approach was developed. There was no difference found between results from PCR and Southern blot analysis. CONCLUSIONS: The PCR method is convenient not only for selection of FRAXA negative patients, but for diagnosis of full mutation and premutation of affected probands.
Subject(s)
Chromosome Fragility , DNA/genetics , Fragile X Syndrome/diagnosis , Polymerase Chain Reaction , Female , Humans , Male , MutationABSTRACT
BACKGROUND: DNA analysis makes it possible to confirm the clinical diagnosis of the majority of cases DMD/BMD and to detect at the same time carries and the prenatal diagnosis for relatives at risk. The objective of the present work was to improve the haplotype analysis and to identify the most frequent deletions in carries. METHODS AND RESULTS: The method is based on the initial amplification of several DNA polymorphisms of CA repetitions and subsequent identification of alleles in the denaturation sequencing polyacrylamide gel using radioactive detection system. The system of CA polymorphisms provides information in the great majority of families, it detects the recombination in the DMD gene, which reduces to a minimum the risk of a diagnostic error and provides valuable information on the carriership of deletion. CONCLUSIONS: The introduction of haplotype analysis of CA repetitions is beyond doubt an asset to the prenatal diagnosis of DMD/BMD and assessment of carriership of this serious hereditary disease. The variability of the length of alleles of these markers improves analysis, prenatal diagnosis and makes it possible to rule out or identify deletion in cca 40% carriers.
