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

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.

Overexpanded CAG repeats in ATN1 cause an Early-Onset Case of Dentatorubral-Pallidoluysian atrophy with novel phenotypes and a literature Review of Chinese patients.

OBJECTIVE: Dentatorubral-pallidoluysian atrophy (DRPLA) is an inherited neurodegenerative disease caused by CAG overexpansion (≥48 tandem copies) in ATN1. The aim of this research was to explore the genetic cause of a large Chinese DRPLA pedigree and to review the characteristics of Chinese DRPLA patients. METHODS: Suspected variants were screened by high-throughput sequencing. The number of CAG repeats was assessed by polymerase chain reaction using FAM-labeled primers followed by capillary electrophoresis. Literature on previously reported DRPLA cases with overexpanded ATN1 CAG repeats in China was reviewed. RESULTS: After contracting a lung infection, the proband suffered early-onset DRPLA symptoms and novel phenotypes, transitioning from insomnia to stupor. The numbers of CAG repeats in the proband, her grandfather, father, mother, brother, and aunt were 8/81, 17/54, 10/57, 8/10, 10/10, and 10/17, respectively. Possible incomplete penetrance was observed in this pedigree. CONCLUSION: We described a large Chinese DRPLA pedigree in which the proband carried the largest CAG expansion reported in China. We also reviewed the characteristics of Chinese DRPLA patients and broadened the phenotypic spectrum.

DRPLA: An unusual disease or an underestimated cause of ataxia in Brazil?

BACKGROUND: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant spinocerebellar ataxia caused by pathological expansion of CAG trinucleotide repeats in the ATN1 gene. Most cases were described in patients from Japanese ancestry who presented with adult-onset progressive cerebellar ataxia associated with cognitive impairment, choreoathetosis and other movement disorders. DRPLA has been rarely described in Brazilian patients. METHODS: We performed a retrospective observational multicentric study including six different Neurology Centers in Brazil. All patients with genetically confirmed diagnosis of DRPLA had their medical records evaluated and clinical, genetic and neuroimaging features were analyzed. RESULTS: We describe of eight Brazilian patients (5 male, 3 female) from four nuclear families with genetically confirmed DRPLA. The most common neurological features included cerebellar ataxia (n = 7), dementia (n = 3), chorea (n = 2), psychiatric disturbances (n = 2), progressive myoclonic epilepsy (n = 2) and severe bulbar signs (n = 1). Progressive myoclonic epilepsy was observed in two juvenile-onset cases before 20-year. A large CAG trinucleotide length was observed in the two juvenile-onset cases and genetic anticipation was observed in all cases. Neuroimaging studies disclosed cerebellar atrophy (n = 6), as well as brainstem and cerebellar atrophy (n = 2) and leukoencephalopathy (n = 1). CONCLUSION: The patients described herein reinforce that clinical features of DRPLA are highly influenced by age of onset, genetic anticipation and CAG repetition lengths. There is a large complex spectrum of neurological features associated with DRPLA, varying from pure cerebellar ataxia to dementia associated with other movement disorders (myoclonus, choreoathetosis). DRPLA is an unusual cause of cerebellar ataxia and neurodegeneration in Brazilian patients.