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Unit Code 81801:
Dentatorubral-Pallidoluysian Atrophy (DRPLA) Gene Analysis

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Useful For

As a diagnostic test for DRPLA.

 

Predictive testing for individuals with a family history of DRPLA. However,

a mutation should be documented first in an affected family member.

Clinical Information

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 the 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 particularly prevalent in Japan

(0.2-0.7 per 100,000). Although rare, DRPLA has been identified in other

populations including Europe and North America.  

 

The underlying mutation in the ATN1 (DRPLA) gene results from

expansion of a trinucleotide (CAG) repeat.  In affected individuals the

CAG repeats range from 48 to 93. 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.

Reference Values

Normal alleles:  7-35 CAG repeats

Abnormal alleles:  49-93 CAG repeats

An interpretive report will be provided.

Interpretation

A written interpretive report is provided. Interpretations take into

account the observed repeat sizes and the reason for referral.

Cautions

The absence of a repeat expansion at the DRPLA locus does

not eliminate the diagnosis of other inherited neurodegenerative

disorders that have overlapping clinical features with DRPLA, such

as Huntington disease or spinocerebellar ataxias.

 

For predictive testing, it is important to first document the presence

of a CAG-repeat amplification in the DRPLA gene in an affected

family member to confirm that molecular expansion is the underlying

mechanism of disease transmission in the family.  

 

In general, predictive testing is not recommended for children or

adolescents.

 

Medical genetic consultation is recommended, particularly for

predictive testing or when the diagnosis is atypical or uncertain.

The complex issues that surround presymptomatic diagnosis of an

untreatable disorder must be addressed.

Special Instructions and Forms

• Molecular Genetics - Congenital Inherited Diseases Patient Information Sheet 

Clinical Reference

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. Advances in Neurology 2002.  89:231-9,

 

3.  Oyanagi S: Hereditary dentatorubral-pallidoluysian atrophy.

      Neuropathology 2000. 20 Suppl:S42-6

Key