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Biomedical subjects

I Vuillaume

Publications and source records attributed to I Vuillaume.

7 recordsLinked to original sources
PubMed2001

Clinical features and genetic analysis of a new form of spinocerebellar ataxia.

BACKGROUND: The autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of disorders. The mutations for SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA-12 are identified and caused by an expansion of a CAG or a CTG repeat sequence of these genes. Six additional loci for SCA4, SCA5, SCA-10, SCA-11, SCA-13, and SCA-14 are mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic etiologies of at least 20% of ADCA have yet to be elucidated. METHODS: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant phenotype for SCA. Direct mutation analysis, repeat expansion detection analysis, and linkage analysis for all known SCA loci were performed. RESULTS: Direct mutational analysis excluded SCA1, 2, 3, 6, 7, 8, and 12; genetic linkage analysis excluded SCA4, 5,10, 11, 13, and 14, giving significant negative lod scores. Examination of the family showed that all affected members had gait ataxia and akinesia with variable features of dysarthria, hyporeflexia, and mild intellectual impairment. Eye movements were normal. Head MRI showed atrophy of the cerebellum without involvement of the brainstem. In 10 parent-child pairs, median onset occurred 10.5 years earlier in offspring than in their parents, suggesting anticipation. CONCLUSION: This family is distinct from other families with SCA and is characterized by cerebellar ataxia and extrapyramidal signs.

Adult↗
PubMed2000

The first identified French family with dentatorubral-pallidoluysian atrophy.

We report the first French family with dentatorubral-pallidoluysian atrophy (DRPLA) in which three members, a 36-year-old woman (proband), her 34-year-old sister, and 14-year-old brother were affected. There was no family history of DRPLA and their father presented at age 66 with pes cavus but without any other neurologic symptoms. Molecular analysis of the DRPLA gene from blood leukocytes showed CAG repeat sizes to be 68/16 in the proband, 62/15 in her father, and 16/16 in her mother. This study provides support for the variable clinical presentation of this disease with incomplete penetrance in the father and demonstrates that DRPLA can be observed in the French Caucasian population.

Adult↗
PubMed2000

Absence of unidentified CAG repeat expansion in patients with Huntington's disease-like phenotype.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded (CAG)n repeat on the huntingtin gene. It is characterised by motor, psychiatric and cognitive disturbances. Diagnosis can be confirmed by direct genetic testing, which is highly sensitive and specific and is now considered definitive. This study focused on 21 patients presenting with a clinical phenotype showing strong similarity to HD, but who do not have an expanded CAG in the huntingtin gene. However, other possible diagnoses could be evoked for most of them. Seven patients (3.5% of our cohort) could be considered as phenocopies of HD with no alternative diagnosis. Samples were screened for other triplet repeat diseases with similar presentation (DRPLA, SCA-1, SCA-2, SCA-3, SCA-6, and SCA-7) and were all negative. The repeat expansion detection technique (RED) was used to detect uncloned CAG repeat expansions and samples were also analysed by polymerase chain reaction for expansions of the polymorphic CAG-ERDA-1 and CTG18.1 trinucleotide repeats. RED expansion (>40 repeats) was detected in only one patient. The results suggest that unstable CAG/CTG repeat expansions corresponding to known or unknown sequences are not involved in the aetiology of HD-like disorders. It is hypothesised that some of these phenocopies could correspond to mutations in other unidentified genes with other unstable repeats (different from CAG) or in unknown genes with other mutations.

Adult↗
PubMed1998

Simple nonisotopic assays for detection of (CAG)n repeats expansions associated with seven neurodegenerative disorders.

To date, eight neurodegenerative diseases, including Huntington's disease, dentatorubral-pallidoluysian atrophy, spinal and bulbar muscular atrophy, and spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, have been proven to be caused by an expanded trinucleotide repeat (CAG)n located within a specific gene for each of these diseases. Except in SCA 6, the CAG repeat is present in approximately 7 to 35 copies in the normal population, whereas patients have CAG expansions of 40 to approximately 75 repeats. Sizing of the repeat length enables molecular diagnosis in affected patients and presymptomatic persons carrying a mutated allele. A molecular protocol for the diagnosis of these diseases was developed based on polymerase chain reaction, denaturing polyacrylamide gel electrophoresis and staining with silver nitrate, and adapted to each disease. This simple and rapid method gives a sensitivity of detection equal to current procedures but avoids isotopic manipulations. Therefore, shorter turnaround time, decreased cost per sample, and simplified screening of these neurodegenerative diseases by PCR-based assays may be attainable using this protocol.

DNA↗
PubMed1998

Genetic polymorphisms adjacent to the CAG repeat influence clinical features at onset in Huntington's disease.

OBJECTIVES: To evaluate possible influences of CCG and delta2642 glutamic acid polymorphisms adjacent to the (CAG)n trinucleotide repeat in Huntington's disease gene IT15 on some clinical features (age and symptoms) at onset. METHODS: 84 patients and a control group of 68 unaffected relatives were studied. Patients all belonged to a group of affected persons tested for molecular confirmation of Huntington's disease. The length of the CAG repeat sequence in the IT15 gene and the adjacent CCG and delta2642 polymorphisms were determined by quantitative polymerase chain reaction. RESULTS: Two intragenic polymorphisms were studied: (CCG)n and delta2642 glutamic acid. Patients were classified firstly according to the size of the CCG rich segment adjacent to the CAG repeat into genotype groups CCG 7/7, 7/8, 7/9, 7/10, and 10/10 and then according to delta2642 polymorphism into genotype groups A/A (absence of the delta2642 deletion), A/B, and B/B (presence of the delta2642 deletion in respectively one and two alleles). The presence of delta2642 mutation was associated with a significant decrease in age at onset, although there was no significant increase in CAG size. A good correlation was found between the (CAG)n trinucleotide repeat size and the age at onset in patients with genotype AA (r2=0.72). Within patients of the A/B genotype group however, a significant correlation was found but with a drop of the r2 value to 0.44. No association was found between age at onset and the CCG polymorphism. Although an increased percentage of patients within the A/A genotype group had a neurological onset, we found no overall significant association between CCG or delta2642 polymorphisms and the nature of symptoms at onset. CONCLUSIONS: The delta2642 glutamic acid polymorphism did not affect CAG repeat size nor the nature of symptoms at onset but seems to influence the age at onset in patients with Huntington's disease.

Adenine↗