Molecular diagnosis of Huntington disease in Brazilian patients

• Published in: Arquivos de neuro-psiquiatria Vol. 58; no. 1; pp. 11 - 17
• Main Authors: Lima E Silva, T C, Serra, H G, Bertuzzo, C S, Lopes-Cendes, I
• Format: Journal Article
• Language: English
• Published: Brazil Academia Brasileira de Neurologia - ABNEURO 01-03-2000; Academia Brasileira de Neurologia (ABNEURO)
• Subjects: Adolescent; Adult; Age of Onset; Alleles; Brazil; Child; Female; Genetic Markers; Genotype; Humans; Huntingtin Protein; Huntington Disease - diagnosis; Huntington Disease - genetics; involuntary movements; Male; Middle Aged; molecular tests; Mutation; Nerve Tissue Proteins; neurodegenerative disorders; NEUROSCIENCES; Nuclear Proteins; Proteins - genetics; PSYCHIATRY; teste molecular; distúrbios do movimento; molecular tests; neurodegenerative disorders; doenças neurodegenerativas; involuntary movements
• ISSN: 0004-282X; 1678-4227; 0004-282X; 1678-4227
• DOI: 10.1590/S0004-282X2000000100002

Huntington disease (HD) is a progressive neurodegenerative disorder with autosomal dominant inheritance, characterized by choreiform movements and cognitive impairment. Onset of symptoms is around 40 years of age and progression to death occurs in approximately 10 to 15 years from the time of disease onset. HD is associated with an unstable CAG repeat expansion at the 5' and of the IT15 gene. We have genotyped the CAG repeat in the IT15 gene in 44 Brazilian individuals (42 patients and 2 unaffected family members) belonging to 34 unrelated families thought to segregate HD. We found one expanded CAG allele in 32 individuals (76%) belonging to 25 unrelated families. In these HD patients, expanded alleles varied from 43 to 73 CAG units and normal alleles varied from 18 to 26 CAGs. A significant negative correlation between age at onset of symptoms and size of the expanded CAG allele was found (r=0.6; p=0.0001); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2=0.4). In addition, we genotyped 25 unrelated control individuals (total of 50 alleles) and found normal CAG repeats varying from 16 to 33 units. The percentage of heterozigocity of the normal allele in the control population was 88%. In conclusion, our results showed that not all patients with the "HD" phenotype carried the expansion at the IT15 gene. Furthermore, molecular diagnosis was possible in all individuals, since no alleles of intermediate size were found. Therefore, molecular confirmation of the clinical diagnosis in HD should be sought in all suspected patients, making it possible for adequate genetic counseling.