Molecular and Clinical Study of Spinocerebellar Ataxia Type 7 in Chinese Kindreds
TLDR
Clinical study revealed that great variation occurred in the age of onset, initial symptoms, and associated signs of spinocerebellar ataxia, and intergenerational instability of the array was associated with the clinical phenomenon of anticipation.Abstract:
Objective: To investigate the clinical and molecular characteristics of spinocerebellar ataxia type 7 (SCA7) in Chinese kindreds. Background: Spinocerebellar ataxia type 7 is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene. Methods: Clinical and related examinations were performed in all affected or at-risk individuals from 4 Chinese families presenting with autosomal dominant cerebellar ataxia and decreased visual acuity. The size of the (CAG)n array of the SCA7 gene was detected by polymerase chain reaction, polyacrylamide gel electrophoresis, and related techniques in the 4 families and 67 healthy controls. The relationship between expanded repeat number and age of onset was statistically analyzed. Results: The SCA7 mutation was identified in 2 families. Clinical study revealed that great variation occurred in the age of onset, initial symptoms, and associated signs. Meanwhile, the analysis of 11 parent-child couples demonstrated the existence of marked anticipation. Some distinct retinal changes were noted in 2 affected patients. All SCA7 patients in our series exhibited expanded CAG repeats, ranging from 44 to 85 repeats, with a strong negative correlation between repeat size and age of onset. Repeat lengths of expanded alleles showed somatic mosaicism in leukocyte DNA. There were some subtle clinical differences between the SCA7-positive and -negative cases. Conclusions: Clinical variation occurred not only among the SCA7 families but also within the same kindred. Meiotic and mitotic instability of the CAG repeat in the SCA7 gene were demonstrated, and intergenerational instability of the array was associated with the clinical phenomenon of anticipation. Arch Neurol. 2000;57:1513-1518read more
Citations
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Journal ArticleDOI
Molecular pathogenesis and cellular pathology of spinocerebellar ataxia type 7 neurodegeneration
TL;DR: It is expected that further study of ataxin-7 normal function, insights into the molecular basis ofSCA7 neurodegeneration, and the development of therapeutic interventions for SCA7 will greatly influence related endeavors directed at other CAG/polyQ repeat diseases.
Book ChapterDOI
The CAG-polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology.
TL;DR: The clinical and molecular genetic features of each distinct disorder are highlighted, and common themes in CAG-polyglutamine disease pathogenesis are discussed, closing with emerging advances in therapy development.
Book ChapterDOI
Spinocerebellar ataxia type 7.
TL;DR: The SCA7 gene encodes a protein of largely unknown function, called ataxin-7, which represents one of the polyglutamine expansion diseases with increase of CAG repeats as mentioned in this paper.
Journal ArticleDOI
Neuro-ophthalmologic features of spinocerebellar ataxia type 7.
TL;DR: Patients with SCA7 often have visual symptoms that may precede, accompany, or follow the onset of ataxic symptoms, which may assist in earlier and more cost-effective diagnosis and permit more effective patient counseling.
Journal ArticleDOI
Molecular Targets and Therapeutic Strategies in Spinocerebellar Ataxia Type 7
TL;DR: A better understanding of the principal molecular mechanisms by which mutant ATXN7 elicits neurotoxicity, and how interconnected pathogenic cascades lead to neurodegeneration is needed for the development of effective therapies is needed.
References
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Journal ArticleDOI
Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion
Gilles David,Nacer Abbas,Giovanni Stevanin,Alexandra Durr,Gaël Yvert,Géraldine Cancel,Chantal Weber,Georges Imbert,Frédéric Saudou,Eric Antoniou,Harry A. Drabkin,Robert M. Gemmill,Paola Giunti,Ali Benomar,Nicholas W. Wood,Merle Ruberg,Yves Agid,Jean-Louis Mandel,Alexis Brice +18 more
TL;DR: Gonadal instability in SCA7 is greater than that observed in any of the seven known neuro-degenerative diseases caused by translated CAG repeat expansions, and is markedly associated with paternal transmissions.
Journal ArticleDOI
The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'.
TL;DR: The clinical features of 11 families containing 73 individuals with dominantly inherited cerebellar ataxia of late onset and an analysis of clustering of clinical features within families using X2 tests suggested that there was little evidence of genetic heterogeneity in the eight kindreds.
Journal ArticleDOI
Molecular and Clinical Correlations in Autosomal Dominant Cerebellar Ataxia with Progressive Macular Dystrophy (SCA7)
Gilles David,Alexandra Durr,Giovanni Stevanin,Géraldine Cancel,Nacer Abbas,Ali Benomar,Samir Belal,Anne-Sophie Lebre,Myriem Abada-Bendib,D. Grid,Monica Holmberg,Mohamed Yahyaoui,Fayçal Hentati,T. Chkili,Yves Agid,Alexis Brice +15 more
TL;DR: The mutation was highly unstable during transmission, with a mean increase of 10 +/- 16 CAG repeats, which was significantly greater in paternal than in maternal transmissions, and correlated well with the marked anticipation observed in the families.
Journal ArticleDOI
Molecular and Clinical Correlations in Spinocerebellar Ataxia 2: A Study of 32 Families
Géraldine Cancel,Alexandra Durr,Olivier Didierjean,Georges Imbert,Katrin Bürk,Agnès Lézin,Samir Belal,Ali Benomar,Myriem Abada-Bendib,Christophe Vial,João Guimarães,Hervé Chneiweiss,Giovanni Stevanin,Gaël Yvert,Nacer Abbas,Frédéric Saudou,Anne-Sophie Lebre,Mohamed Yahyaoui,Fayçal Hentati,Jean-Claude Vernant,Thomas Klockgether,Jean-Louis Mandel,Yves Agid,Alexis Brice +23 more
TL;DR: The frequency of several clinical signs such as myoclonus, dystonia and myokymia increased with the number of CAG repeats whereas the frequency of others was related to disease duration, and instability was confirmed by the high degree of gonadal mosaicism observed in sperm DNA of one patient.