Huntington disease and Huntington disease‐like in a case series from Brazil

Abstract

The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

Genetic aspects of Huntington's disease in Latin America. A systematic review

“…AO and correlations with the expanded CAG repeats, proportion of juvenile cases, and homozygote cases Twelve publications reported mean AO, and 10 of them estimated the correlation between AO and expanded (26) noted that AO association with the expanded repeat was stronger in those individuals with expansions longer than 50 repeats. Other reports did not stratify their samples in this way, and showed a single line across the entire range of CAG repeat lengths (32,40,41,43,48,50,52,54,55). Figure 2 illustrates some of these findings.…”

“…Three studies have addressed the frequency of IAs in control groups, and other seven studies described IAs found in normal chromosome of their HD case series. Proportion of IAs varied between 2 and 5% of the normal chromosomes analyzed (26,32,(40)(41)(42)(43)50), with two exceptions, where extremely high proportions of IAs seemed to be due to recruitment of several individuals per family, and to small sample sizes (48,51).…”

“…Twelve LA studies described the distribution of expanded CAG repeats among HD patients (Table S2). Excluding one outermost result likely to be due to ascertainment bias favoring early onset patients (48), the obtained average measurements varied from 41 to 47 CAG repeats (26,32,33,(40)(41)(42)(43)(49)(50)(51)(52).…”

Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress

“…Putative binding factors were predicted using SpaMo directly from the DREME suite software package and are listed in the tables shown with their putative transcription factors. The literature (Ref) links of each TF to psychiatric disorders are shown: Scz (schizophrenia); BP (Bipolar Disorder); MDD (Major Depressive Disorder); Epi (Epilepsy); ND (Neuronal Differentiation); OCD (Obsessive Compulsive Disorder) (Aston et al, 2005; Basmanav et al, 2015; Butts et al, 2014; Castilhos et al, 2014; Chen et al, 2014b; Chiang et al, 2015; Forero et al, 2016; Forrest et al, 2013; Goes et al, 2015; Grados et al, 2014; Gurung and Prata, 2015; Hattori et al, 2014; Johansson et al, 2016; Jukic et al, 2015; Keyes et al, 2015; Kim et al, 2014; Le-Niculescu et al, 2009; Lisowski et al, 2013; Mencarelli et al, 2008; Nestadt et al, 2012; Rivolta et al, 2014; Rotheram-Fuller et al, 2010; Schlaudraff et al, 2014; Shi et al, 2016; Wang et al, 2014; Wei et al, 2015; Wockner et al, 2014). …”

Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype

“…JPH3 expansion mutations are found in as few as 1% of individuals with clinically or pathologically defined HD without an HTT mutation. It was recognized early on that most of the individuals with HDL2 have definite or likely African ancestry, including African–American individuals, a Mexican family, a Moroccan individual, and cases from Brazil and Venezuela [Holmes et al, ; Stevanin et al, ; Rodrigues et al, ; Paradisi et al, ; Castilhos et al, ]. An early pilot study [Krause et al, ] and subsequent case identification suggested that the mutation may be particularly frequent in South African black or mixed ancestry patients with a Huntington disease phenotype [Bardien et al, ; Magazi et al, ].…”