Dentatorubral‑Pallidoluysian Atrophy Repeat Analysis

Casandra

Casandra Test Code GE13660Version 1 (DRAFT)

Performing Lab

Lab GeneDxLab Test ID N/A

Dentatorubral‑Pallidoluysian Atrophy Repeat Analysis

Clinical Use

Use

Dentatorubral‑pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat in exon 5 of the ATN1 gene. Clinical presentation varies by age of onset with juvenile-onset featuring ataxia, myoclonus, seizures, and intellectual deterioration, and adult-onset presenting with ataxia, choreoathetosis, dementia, and psychiatric symptoms. The test analyzes the CAG repeat region in ATN1 to distinguish normal, mutable normal, incompletely penetrant, and pathogenic allele ranges, assisting in diagnosis, prognosis, and family counseling. Anticipation is a known phenomenon for this repeat expansion disorder. (Based on GeneDx test method documentation)

Special Instructions

ORDERING: Use standard GeneDx test requisition procedures. The test is also known by synonyms DRPLA, Haw River syndrome, Naito‑Oyanagi disease (NOD). Variants with ≤100 repeats are measured via PCR fragment analysis; alleles >100 repeats detected via repeat‑primed PCR but exact repeat count not determined. Southern blot needed for alleles with >100 repeats and is not part of this test. Accuracy for ≤50 repeats is ±2 repeats; for 51–100 repeats accuracy is ±5 repeats.

Limitations

Accuracy of repeat sizing: fragment analysis provides ±2 repeats for sizes ≤50 and ±5 repeats for 51–100; alleles >100 repeats cannot have exact repeat number determined by this test. Southern blot, required for >100 repeats, is not performed as part of this assay. Clinical interpretation must consider incomplete penetrance for alleles of 36–47 repeats and often anticipatory expansion in transmission, especially paternal. Technical sensitivity depends on phenotype but all pathogenic expansions are detectable with fragment analysis; internal standards used to assure performance.

Test Details