Dentatorubral-Pallidoluysian Atrophy (DRPLA) Gene Analysis
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized by ataxia, choreoathetosis, dementia, and psychiatric disturbance in adults and ataxia, myoclonus, seizures, and progressive intellectual deterioration in children. Characteristic neuropathologic observations include degeneration of the dentatorubral and pallidoluysian systems of the central nervous system.
The prevalence of DRPLA depends on the geographic and ethnic origin of the population being studied. DRPLA was first described in a European individual without a family history; however, it is predominantly found as an inherited condition and is most prevalent in Japan (0.2-0.7 per 100,000). Although rare, DRPLA has been identified in other populations including Europe and North America.
DRPLA is caused by an expansion of the CAG trinucleotide repeat in the ATN1 (DRPLA) gene. This trinucleotide repeat is polymorphic in the general population, with the number of repeats ranging from 7 to 35. In affected individuals the CAG expansion ranges from 48 to 93 repeats. As with other trinucleotide repeat disorders, anticipation is frequently observed, and larger CAG expansions are associated with earlier onset and a more severe and rapid clinical course. In DRPLA, the observed anticipation appears to be significantly greater in paternal transmissions.
Molecular confirmation of a diagnosis of dentatorubral-pallidoluysian atrophy (DRPLA) for symptomatic patients
Predictive testing for individuals with a family history of DRPLA and a documented expansion in the ATN1 gene in an affected family member
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
For predictive testing, it is important to first document the presence of a CAG-repeat amplification in the ATN1 gene in an affected family member to confirm that molecular expansion is the underlying mechanism of disease in the family.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Predictive testing of an asymptomatic child is not recommended.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
The absence of an expansion in the ATN1 gene does not eliminate the diagnosis of other inherited neurodegenerative disorders that have overlapping clinical features with DRPLA, such as Huntington disease or spinocerebellar ataxias.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Normal alleles: 7-35 CAG repeats
Abnormal alleles: 49-93 CAG repeats
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Ikeuchi T, Onodera O, Oyake M, et al: Dentatorubral-pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation. Semin Cell Biol 1995;6:37-44
2. Tsuji S: Dentatorubral-pallidoluysian atrophy: clinical aspects and molecular genetics. Ad Neurol 2002;89:231-239
3. Oyanagi S: Hereditary dentatorubral-pallidoluysian atrophy. Neuropathology 2000 20 Suppl:S42-6