Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7)

Autor: Géraldine Cancel, Fayçal Hentati, Monica Holmberg, D. Grid, Mohamed Yahyaoui, Yves Agid, Anne-Sophie Lebre, T. Chkili, Alexis Brice, Myriem Abada-Bendib, Gilles David, Giovanni Stevanin, Samir Belal, Ali Benomar, Nacer Abbas, Alexandra Durr
Rok vydání: 1998
Předmět:
Male
Germline mosaicism
Severity of Illness Index
Macular Degeneration
Africa
Northern
Belgium
Trinucleotide Repeats
Autosomal dominant cerebellar ataxia
Age of Onset
Israel
Child
Genetics (clinical)
Genes
Dominant
Spinocerebellar Degenerations
Genetics
Ophthalmoplegia
Mosaicism
Exons
Syndrome
General Medicine
Middle Aged
Macular dystrophy
Magnetic Resonance Imaging
Spermatozoa
Scoliosis
Child
Preschool
Olivopontocerebellar Atrophies
Spinocerebellar ataxia
Female
Chromosomes
Human
Pair 3
France
medicine.symptom
Adult
medicine.medical_specialty
Adolescent
Biology
Internal medicine
medicine
Humans
Molecular Biology
Alleles
Aged
Cerebellar ataxia
Infant
Dystrophy
medicine.disease
Urinary Incontinence
Endocrinology
Anticipation (genetics)
Deglutition Disorders
Trinucleotide repeat expansion
Fecal Incontinence
Zdroj: Human Molecular Genetics. 7:165-170
ISSN: 1460-2083
DOI: 10.1093/hmg/7.2.165
Popis: Spinocerebellar ataxia 7 (SCA7) is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene. We have analyzed the SCA7 mutation in 19 families and one isolated case of various geographical origins, presenting with autosomal dominant cerebellar ataxia with progressive macular dystrophy. The SCA7 CAG repeat was expanded in 77 patients and in 11 at-risk individuals, with alleles containing from 37 to 130 repeats, demonstrating that SCA7 is genetically homogeneous. Repeats on normal alleles contained from 7 to 35 CAGs. There was a strong negative correlation (r = -0.84) between the age at onset and the size of the CAG repeat expansion in SCA7 patients. Larger expansions were associated with earlier onset, a more severe and rapid clinical course, and a higher frequency of decreased vision, ophthalmoplegia, extensor plantar response and scoliosis. The frequency of other clinical signs such as dysphagia and sphincter disturbances increased with disease duration. The mutation was highly unstable during transmission, with a mean increase of 10 +/- 16 CAG repeats, which was significantly greater in paternal (15 +/- 20) than in maternal (5 +/- 5) transmissions. This correlated well with the marked anticipation (19 +/- 13 years) observed in the families. Gonadal mosaicism, observed in the sperm of a patient, was particularly important, with expanded alleles ranging from 42 to >155 CAG repeats. The degree of instability during transmission, resulting mostly in expansions, is greater than in the seven other neurodegenerative disorders caused by polyglutamine expansions.
Databáze: OpenAIRE
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