Sizing of the CAG trinucleotide repeat expansion in the Huntington gene
Performing Laboratory / Facility
UCLA Medical Center Clinical Laboratory (CHS)
Performing Section
Molecular Pathology
Availability
Monday through Friday, 0700-1700
Turnaround Time
14 days from receipt of specimen in performing lab
Methodology
The size of the trinucleotide repeat is determined by performing polymerase chain reaction amplification using fluorescent labeled primers that flank the trinucleotide repeats followed by capillary electrophoresis. The number of repeats can be determined from the peak size by comparison with known size markers. Normal individuals will have allele sizes of 11-28 repeats. Most people will have two different sized bands in this range, but a few will be homozygous for the same size band. Huntington chromosomes will produce bands from 40-120 repeats.
Use
Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disorder which usually presents by the age of 40-50 and is characterized by progressive disordered movements (chorea), psychiatric alterations, and cognitive decline. HD is caused by an expansion of a CAG trinucleotide repeat within a novel gene on 4p16.3. Normal chromosomes usually have 11-35 repeats, while Huntington chromosomes will have larger than or equal to 40, up to 100 or more, repeats. Repeat sizes between 36-39 have variable penetrance. The CAG repeat length shows a highly significant correlation with age of onset of clinical features and this association is particularly evident for persons with juvenile onset HD where CAG expansion is usually >100 repeats.
Limitations
Repeat numbers in the range of 35-39 have been shown to have a variable phenotype and thus should be interpreted in the context of an affected relative.
Additional Information
Presymptomatic testing is generally offered through the Medical Genetics Clinic and involves stringent informed consent procedures as well as pre- and post-test genetic counseling. These requirements are not mandatory for diagnostic testing in symptomatic individuals.
Sizing of the CAG trinucleotide repeat expansion in the Huntington gene
Performing Laboratory / Facility
UCLA Medical Center Clinical Laboratory (CHS)
Performing Section
Molecular Pathology
Availability
Monday through Friday, 0700-1700
Turnaround Time
14 days from receipt of specimen in performing lab
Methodology
The size of the trinucleotide repeat is determined by performing polymerase chain reaction amplification using fluorescent labeled primers that flank the trinucleotide repeats followed by capillary electrophoresis. The number of repeats can be determined from the peak size by comparison with known size markers. Normal individuals will have allele sizes of 11-28 repeats. Most people will have two different sized bands in this range, but a few will be homozygous for the same size band. Huntington chromosomes will produce bands from 40-120 repeats.
Use
Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disorder which usually presents by the age of 40-50 and is characterized by progressive disordered movements (chorea), psychiatric alterations, and cognitive decline. HD is caused by an expansion of a CAG trinucleotide repeat within a novel gene on 4p16.3. Normal chromosomes usually have 11-35 repeats, while Huntington chromosomes will have larger than or equal to 40, up to 100 or more, repeats. Repeat sizes between 36-39 have variable penetrance. The CAG repeat length shows a highly significant correlation with age of onset of clinical features and this association is particularly evident for persons with juvenile onset HD where CAG expansion is usually >100 repeats.
Limitations
Repeat numbers in the range of 35-39 have been shown to have a variable phenotype and thus should be interpreted in the context of an affected relative.
Additional Information
Presymptomatic testing is generally offered through the Medical Genetics Clinic and involves stringent informed consent procedures as well as pre- and post-test genetic counseling. These requirements are not mandatory for diagnostic testing in symptomatic individuals.
