RESUMEN
BACKGROUND: Huntington disease-like 2 (HDL2) is a neurodegenerative disorder, affecting only individuals of African ancestry. Full penetrance occurs in individuals with 40 repeats or more. OBJECTIVE: To describe the phenotypic variability of HDL2 in a group of mixed ancestry individuals from South Africa. METHODS: Eight patients were assessed with analysis of repeat size and magnetic resonance brain imaging. We applied the Unified Huntington's Disease Rating Scale (UHDRS), but in deceased patients (4), this was estimated from video material. RESULTS: Cognitive domains were more severely affected than motor; UHDRS motor scores were notable for bradykinesia, and to a slightly lesser extent, for rigidity and dystonia; a single patient had marked chorea. Repeat lengths ranged from 45 to 63 (median, 52). CONCLUSION: This South African group of mixed ancestry HDL2 individuals presented with severe cognitive and behavioral impairments, with lesser degrees or absence of chorea. This presentation is possibly related to large repeat sizes.
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Imagen por Resonancia Magnética , Humanos , Masculino , Sudáfrica/epidemiología , Femenino , Persona de Mediana Edad , Adulto , Población Negra/genética , Enfermedad de Huntington/genética , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/etnología , Anciano , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Trastornos Heredodegenerativos del Sistema Nervioso/diagnóstico , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patología , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Corea/genética , Corea/diagnóstico , Trastornos del Conocimiento , DemenciaRESUMEN
BACKGROUND: The prevalence of Parkinson's disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. METHODS: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2's protein structure was investigated by molecular modelling. RESULTS: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. CONCLUSIONS: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.
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Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedad de Parkinson/genética , ATPasas de Translocación de Protón/genética , Adulto , Anciano , Anciano de 80 o más Años , Población Negra/genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Anotación de Secuencia Molecular , Mutación Missense , Nigeria/epidemiología , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/patología , Mutación Puntual , Sudáfrica/epidemiologíaRESUMEN
INTRODUCTION: This study seeks to determine whether the use of Eulerian video magnification (EVM) increases the detection of muscle fasciculations in people with amyotrophic lateral sclerosis (PALS) compared with direct clinical observation (DCO). METHODS: Thirty-second-long video recordings were taken of 9 body regions of 7 PALS and 7 controls, and fasciculations were counted by DCO during the same 30-s period. The video recordings were then motion magnified and reviewed by 2 independent assessors. RESULTS: In PALS, median fasciculation count per body region was 1 by DCO (range 0-10) and 3 in the EVM recordings (range 0-15; P < 0.0001). EVM revealed more fasciculations than DCO in 61% of recordings. In controls, median fasciculation count was 0 for both DCO and EVM. DISCUSSION: Compared with DCO, EVM significantly increased the detection of fasciculations in body regions of PALS. When it is used to supplement clinical examination, EVM has the potential to facilitate the diagnosis of ALS. Muscle Nerve 56: 1063-1067, 2017.