Huntington s Disease: The Need for a Standard Reference Material to Provide Quality Control for the Accurate Detection of the Number of Causal Trinucleotide Repeats

Published

October 16, 2008

Author(s)

Barbara C. Levin, Kristy L. Richie

Abstract

Huntington disease (HD) is a neurodegenerative disease with prevalence rates that vary in different parts of the world, but average from 4 to 7 per 100,000 individuals. The onset of symptoms usually begins in middle age, although approximately 5% become symptomatic as juveniles. Death occurs about 15 years following the onset of symptoms, the most prevalent of which include choreic movements, cognitive decline and psychiatric changes. HD is an autosomal dominant inherited disease that, in 1993, was discovered to be associated with an expansion of a trinucleotide (CAG) repeat located on chromosome 4 at position 4p16.3. The HD gene contains 67 exons (the CAG triplet repeat is located in exon 1) and more than 200 kb. This gene, also designated IT-15, codes for the huntingtin protein with a molecular weight of 350 kDa and 3136 amino acids. More than 99% of tested HD patients have 40 or more CAG triplet repeats and therefore, targeted mutational analysis is better than 99 % sensitive. Individuals with 26 triplet repeats or less are normal; whereas, 27 to 35 CAG repeats are rarely observed and do not seem to result in the disease, but may expand and produce HD in future generations. Individuals with 36 to 39 repeats may or may not manifest HD symptoms. The importance of standardizing methodology to determine the accurate number of CAG repeats and thereby preventing false positive or false negative results when conducting predictive or prenatal testing of at-risk individuals has been emphasized by the CAP/ACMG Biochemical and Molecular Genetics Resource Committee since 1998. The National Institute of Standards and Technology plans to develop a Standard Reference Material to help fulfill this need of the clinical testing laboratories for positive and negative controls.

Citation

Clinical Chemistry

Pub Type

Journals

Keywords

autosomal dominant, HD, Huntington, Huntington Chorea, Huntington Disease, trinucleotide CAG repeat, trinucleotide CCG repeat, triplet repeat

Citation

Levin, B. and Richie, K. (2008), Huntington s Disease: The Need for a Standard Reference Material to Provide Quality Control for the Accurate Detection of the Number of Causal Trinucleotide Repeats, Clinical Chemistry (Accessed December 12, 2024)