Dentatorubro-Pallidoluysian Atrophy (DRPLA) among 700 Families with Ataxia in Brazil

Abstract

Dentatorubro-pallidoluysian atrophy (DRPLA) is a spinocerebellar ataxia (SCA) very rare in non-Asian populations. To date, DRPLA was undetected in the general Brazilian population. Adult-onset ataxic patients have been recruited from several Brazilian neurology and neurogenetics centers. CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17 and DRPLA associated genes, and ATTCT expansions at SCA10 gene were studied. A single DRPLA case detected is reported. Proband was a 69-year-old Brazilian woman of mixed ancestry, with a late-onset pure ataxia: her alleles at the associated gene, ATN1, presented 14/52 CAG repeats. History of gait ataxia and dementia was observed in two out of six siblings but was absent in her parents. This was the single DRPLA diagnosis obtained from 700 Brazilian unrelated cases with adult-onset ataxia, 487 of them with clear autosomal dominant inheritance. DRPLA accounted for 0.14% of all adult-onset ataxia cases and for 0.2% of families with autosomal dominant inheritance. Normal CAG repeats at ATN1 had a median (range) of 14 (5-20) repeats in other 410 Brazilian chromosomes. DRPLA is quite rare in Brazilian SCA families, which is consistent with the lack of large normal alleles in our population.

DRPLA: understanding the natural history and developing biomarkers to accelerate therapeutic trials in a globally rare repeat expansion disorder

“…In Singapore, Korea and China, the frequencies of DRPLA have been found to be 3.4%, 3.4%, and 1%, respectively [ 42 , 50 , 111 ]. In South America, the DRPLA frequency has found to be 0.14% and 3.1% in SCA cohorts from Brazil and Venezuela, respectively [ 8 , 65 ]. In Europe, findings have been variable, with reports of the frequency in Portuguese cohorts with autosomal dominant ataxias of DRPLA ranging from 4 to 11.2%, whilst in Spain, the frequency was reported as 3.3% [ 18 , 39 , 93 ].…”

The Geographic Diversity of Spinocerebellar Ataxias (SCAs) in the Americas: A Systematic Review

“…Subphenotype 2 was the most common, with ataxia and pyramidal findings (67.5%), followed by subphenotype 3 with ataxia and peripheral signs (13.3%), and subphenotype 6 with pure cerebellar syndrome in 7.2% . Only 1 family with DRPLA has been reported in Brazil, among 487 patients with autosomal dominant ataxias (0.2%) . This family had 6 affected members, all with late‐onset ataxia and associated with dementia in 2.…”

Dentatorubral-Pallidoluysian Atrophy: An Update

“… 7 Worldwide the prevalence of SCAs is 2.7 per 100,000, 24 and within these cohorts the highest frequency of DRPLA is seen among Japanese groups (7–20%), with lower rates in other Asian populations (Singapore, 6%; Korea, 3%). 25 In European populations, DRPLA has a frequency of 2–4% in Portuguese SCA families, 8 0.25–1% in other SCA samples of European descent, 23 , 26 , 27 , and 0.14–3.1% in Latin-American SCA cohorts. 25 , 28 However, these estimates may be higher in some populations, potentially because of a higher proportion of “high-normal” repeat lengths or sampling variation.…”

“… 25 In European populations, DRPLA has a frequency of 2–4% in Portuguese SCA families, 8 0.25–1% in other SCA samples of European descent, 23 , 26 , 27 , and 0.14–3.1% in Latin-American SCA cohorts. 25 , 28 However, these estimates may be higher in some populations, potentially because of a higher proportion of “high-normal” repeat lengths or sampling variation. 7 Longer repeat lengths appear more commonly in populations of Japanese origin than in Caucasians.…”