Huntington's disease like phenotype: new data from Brazil and what we know between heaven and earth.

Editorial Huntington's disease like phenotype New data from Brazil and what we know between heaven and earth. Huntington's disease (HD) is an auto-somal dominant neurodegenerative disorder , characterized by involuntary movements , predominantly chorea, associated to behavioral and cognitive impairment 1,2. HD is caused by expansion of a CAG repeat in the coding region of the IT15 gene located on chromosome 4p16.3, that encodes a protein called huntingtin. The expanded polyglutamine tract encoded by the CAG repeat expansion is toxic and critical in HD pathogenesis 2. The most prominent neuropathological finding is atrophy of the striatum 1,2. The prevalence of HD in the Caucasian population ranges from 0.5-1 in 10,000. Mean age at onset is between 35 and 50 years, and the disease progresses inexorably and has a mean duration of 17-20 years, and no effective treatment is currently available 2. In general about 1% of all cases of clinically or pathologically defined HD do not have the HD mutation and theses cases are known as Huntington's disease-like phenotype (HDL) or HD phenocopies 3. To date, there are 4 phenocopies known as HDL1, 2, 3, and 4. HDL1 is caused by a octapeptide repeat insertion in gene encoding prion protein, HDL2 is associated to triplet repeat expansion in gene encoding junctophilin-3, HDL3 is a autosomal recessive disease, which a causative mutation is unknown, and HDL4 or spinocere-bellar ataxia type 17 (SCA17) is caused by triplet repeat expansion in gene encoding TATA-box binding protein (TBP) 3-9. Additionally , dentatorubral-pallidoluysian atrophy (DRPLA), caused by a triplet repeat expansion in gene encoding atro-phin-1, is associated to HD phenocopies. Others diseases that may have a HD phe-nocopies are neuroacanthocytosis (mutation in gene encoding chorein), neurode-generation with brain iron accumulation (NBIA) or pantothenate kinase-associated neurodegeneration (PKAN), caused by mutations in the PANK2 gene, neuroferri-tinopathy (mutations in gene encoding fer-ritin light-chain), and spinocerebellar atax-ias (SCAs) types 1 and 3 3-9. Margolis et al. in 2004 studied HDL2 in a series of patients with HD or HDL of North America and Japan, and demonstrated that HDL2 is very rare, with a frequency of 0 to 15% among patients, exclusively found in patients with African ancestry 10. Other studies performed in other countries, including Portugal, Japan, and Poland, did not detected any case of HDL2 10-12. In Latin America, particularly in Brazil, Teive et al. described in 2007 the first case of HDL2 in a patient without African …