Elison Sarapura-Castro

Spinocerebellar ataxia type 27B (SCA27B) is a recently described autosomal dominant ataxia caused by a pathogenic GAA repeat expansion in the FGF14 gene. The frequency and the distribution of FGF14 repeat alleles remain largely unexplored in underrepresented populations, particularly in Latin America. To investigate the frequency of SCA27B and characterize the allelic distribution of the GAA-FGF14 microsatellite locus in a Peruvian cohort of individuals with ataxia of unknown molecular etiology. We analysed a cohort of affected individuals evaluated at a referral center for neurogenetic disorders in Peru. All individuals underwent standardized neurological assessment, as well as molecular analysis of the GAA-FGF14 repeat locus using repeat-primed and long-range PCR-based approaches. One genetically confirmed case of SCA27B was identified, corresponding to a frequency of 0.6% (1/167) in this cohort. Most alleles (91.61%) were within the non-pathogenic range (< 250 repeats), 85.3% of them with less than 30 repeats. Notably, 16.17% of individuals carried non-GAA-pure expanded alleles with a complex [(GAA)_n(GCA)_m]_z repeat structure, currently considered non-pathogenic. These alleles were not associated with a typical SCA27B phenotype. SCA27B appears to be a rare cause of hereditary ataxia in the Peruvian population. The high prevalence of non-GAA-pure expanded alleles and the distinct FGF14 allelic distribution illustrates the allelic diversity of the FGF14 GAA locus. These findings highlight the importance of investigating diverse populations to better understand the genetic mechanisms underlying SCA27B and other repeat expansion-associated ataxias.

Background: Spinocerebellar ataxia type 10 (SCA10 or ATX‐ ATXN10 ) is typically attributed to large intronic ATTCT repeat expansions in ATXN10 , yet interpretation is complicated by repeat interruptions, reduced penetrance, and assay limitations. Cases: We describe three patients referred for SCA10 evaluation in whom ATXN10 repeat‐primed PCR (RP‐PCR) reported “>32 repeats, probable pathogenic.” Targeted long‐read sequencing (LRS) identified two individuals with intermediate, mixed repeat tracts (~100–150 repeats) and one individual with a very large, highly pure ATTCT expansion (~1127 repeats). Each phenotype was explained by an alternative disorder: spastic ataxia syndrome caused by biallelic pathogenic FA2H variants (HSP/ATX‐ FA2H ), full‐penetrance ATXN3 CAG expansion consistent with SCA3/ATX‐ ATXN3 , and clinically established MSA‐C. Literature Review: We identified three studies reporting four ATX‐ ATXN10 cases coexisting with Huntington's disease (one case) and SCA2/ATX‐ ATXN2 (three cases). Conclusion: Our three cases suggest that intermediate ATXN10 alleles in the 100–150 range may not be pathogenic and large ATXN10 expansions remain probably pathogenic in most patients with a compatible autosomal‐dominant ataxia phenotype. Comprehensive genetic testing beyond RP‐PCR is necessary for accurate diagnosis.

Objetivo: Comparar la frecuencia de crisis epilépticas entre pacientes con SCA10 y otras SCA en una muestra de la población peruana. Materiales y métodos: Estudio observacional con componente retrospectivo con revisión de historias clínicas y prospectivo con entrevista previo consentimiento informado. Se reclutaron pacientes con diagnóstico genético de SCA atendidos entre enero de 2014 y diciembre de 2023 en un centro de referencia nacional de Perú. Resultados: Se identificaron 125 casos/87 familias con diagnóstico de seis tipos de SCA (SCA1, SCA2, MJD/SCA3, SCA6, SCA7 y SCA10), con una frecuencia global de 11,2 % de crisis epilépticas. Estas predominaron en el subgrupo SCA10 (16 %), en contraste con el subgrupo de otras SCA (4 %), donde se hallaron dos casos de SCA2 con crisis epilépticas. Conclusiones: Las crisis epilépticas son significativamente más frecuentes en SCA10 respecto de las otras SCA en la población estudiada. Predominan las crisis de inicio desconocido tipo motor tónico-clónicas en SCA10 y las crisis de inicio focales motoras en SCA2, ambas con buena respuesta a medicación anticrisis.

Las ataxias hereditarias representan un grupo diverso de enfermedades neurogenéticas caracterizadas por alteraciones en la coordinación motora, debido a la disfunción del cerebelo o sus vías asociadas. Estas enfermedades incluyen formas autosómicas dominantes, recesivas, ligadas al cromosoma X y mitocondriales. El diagnóstico y el tratamiento son complejos, más aún en regiones con recursos limitados como Perú y otros países de Latinoamérica, donde se presentan desafíos adicionales. Esta revisión propone un enfoque diagnóstico estructurado para las ataxias hereditarias que consiste en cinco ejes: 1) confirmación del tipo de ataxia (cerebelosa o no cerebelosa); 2) edad de inicio; 3) forma de presentación (predominantemente pura o plus); 4) historia familiar; y 5) exclusión de causas reversibles o secundarias. Los estudios auxiliares más útiles en el diagnóstico diferencial, dependiendo de la información recolectada de los 5 ejes, incluyen análisis séricos, neuroimagen, estudios neurofisiológicos, evaluaciones neurooftalmológicas, pruebas vestibulares y estudios genéticos (genes específicos, paneles genéticos, exoma y genoma clínico). La implementación de un enfoque diagnóstico basado en estos pilares optimiza tanto el diagnóstico como el manejo clínico de esta enfermedad, especialmente en contextos con recursos limitados.

La distrofia miotónica tipo 1 (DM1) es una enfermedad neuromuscular hereditaria autosómica dominante de carácter sistémico, caracterizada por debilidad muscular progresiva, miotonía y cataratas. Además, puede comprometer los sistemas cardiovascular, endocrino y nervioso central. En este reporte presentamos tres casos de DM1 con afectación significativa del sistema nervioso central, evidenciada por alteraciones estructurales en imágenes de resonancia magnética cerebral, deterioro cognitivo, epilepsia y cambios conductuales. Se destaca la importancia de una evaluación multidisciplinaria que integre valoraciones neuropsiquiátricas y estudios de neuroimagen como parte esencial del manejo integral de esta afección.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal-dominant disorder caused by intronic expansions of pentanucleotide repeats in the ATXN10 gene. While various repeat motifs have been described, emerging evidence suggests that specific repeat motifs, rather than repeat length alone, can modify disease features such as seizure prevalence and penetrance. We used a novel multiplex 20-gene panel with Cas9-targeted, amplification-free long-read sequencing (LRS) and optical genome mapping to elucidate ATXN10 repeat motif patterns and investigated genotype-phenotype correlations in index cases of 6 multigenerational SCA10 kindreds from Peru. We detected ATXN10 repeat expansions ranging from 990 to 2,002 pentanucleotide repeats (4.9–10 kb) across 6 families. It is important to note that we identified 3 mixed repeat motif patterns and ratios of (ATTCT)_n(ATTCC)_n, which were associated with differences in age at disease onset and anticipation. Our key novel finding is the prominence of the alternate ATTCC motif alongside the common ATTCT motif. While repeat length alone does not appear to drive disease onset in SCA10, we uncovered that the ratio of the ATTCC motif within distinct repeat patterns might correlate with disease onset. These findings underscore the need to adapt LRS clinical workflows to fully characterize large repeat expansions at the nucleotide level.

Background: The global prevalence of Parkinson's disease (PD) is estimated to be 315 per 100,000 inhabitants, with variations across regions and depending on the epidemiological methods used. Door‐to‐door prevalence studies in Andean communities are notably underrepresented in the literature. Objective: The aim of this study was to estimate the PD prevalence in Jauja. Methods: A cross‐sectional community‐based door‐to‐door prevalence study was conducted from April 2018 to September 2019. We used a Spanish version of the 9‐item screening questionnaire (9‐item SQ). Trained interviewers conducted face‐to‐face screening surveys. Participants presenting “suspected parkinsonism” underwent further neurological assessment. PD cases responded to the LARGE‐PD questionnaire and “pesticide exposure questionnaire.” We calculated the crude prevalence, gender‐ and age‐specific rates, and age‐adjusted rates. Results: Out of 2527 eligible individuals, 1960 completed the screening survey. Of these, 563 were selected for neurological assessment, and 337 underwent neurological examination. PD was confirmed in 21 individuals, 16 of whom were identified using the 9‐item SQ with a crude prevalence of 816/100,000. We observed higher rates of PD in older age groups and in males compared to females (1.6 vs. 0.3%, P < 0.05). The age‐standardized prevalence was 566/100,000 (95% confidence interval [CI]: 496.6–635.2). Among PD cases, the most common environmental exposures were living near farming fields and pesticide exposure. Conclusions: The observed prevalence of PD in this town in the central highlands of Peru aligns with previous reports, with notably higher rates among individuals over the age of 80. Further prospective studies are warranted to investigate the potential influence of environmental factors on PD prevalence in this region.

The Spinocerebellar Ataxias (SCAs) are a group of autosomal dominant neurodegenerative disorders characterized by progressive cerebellar ataxia, affecting motor coordination. SCAs are reported globally with large geographical and ethnic differences. This systematic review and meta-analysis aimed to update the frequency, and geographic distribution of SCAs in Latin America, including recently identified SCAs like SCA27B. We conducted a systematic search in PubMed, Scopus, LILACS, SciELO, and Web of Science databases, including studies published from inception to January 2025. We included 27 studies for the systematic review and 18 studies for the meta-analysis that met the inclusion criteria, representing a total of 5859 participants across eleven countries. Our meta-analysis revealed that about 50% (95% CI 26–74%) of hereditary ataxias in Latin America were confirmed to have a genetic diagnosis of SCA. The included participants with a known SCA have the following proportions: MJD/SCA3 (15%), SCA2 (11%), SCA7 (4%), SCA10 (3%), and SCA1 (3%). Geographic distributions were notable, MJD/SCA3 in Brazil, SCA2 in Cuba, Argentina and Mexico, SCA10 predominating in Peru, and SCA7 in Venezuela. Recently identified SCA types, like SCA27B and one case of SCA4, were identified in Brazil. In 22 countries there are no published studies on the epidemiology of SCAs. The distribution of SCAs in Latin America reflects the influence of historical migrations, founder effects, and ancestries, emphasizing regional heterogeneity. Our findings underscore the critical need for further epidemiological studies, particularly in understudied countries in the region.

Objectives: Spinocerebellar ataxia type 10 (SCA10) is an autosomal-dominant disorder caused by large intronic expansions of pentanucleotide repeats in the ATXN10 gene. While various repeat motifs have been described, emerging evidence suggests that specific repeat motifs—rather than merely repeat length alone—can significantly modify disease features such as seizure prevalence and penetrance. Methods: We employed a novel multiplex 20-gene panel with Cas9-targeted, amplification-free long-read sequencing and optical genome mapping to elucidate ATXN10 repeat motif patterns and investigate potential genotype-phenotype correlations in index cases of six clinically well-characterized multigenerational SCA10 kindreds from Peru. Results: We detected ATXN10 repeat expansions ranging from 990 to 2002 pentanucleotide repeats (4.9 to 10 kb expansions) across six families. Importantly, we identified three mixed repeat motif patterns and ratios of (ATTCT)ₙ(ATTCC)ₙ, which were associated with differences in age at disease onset and anticipation. Discussion: Specific ATXN10 repeat motif patterns and (ATTCT)_n(ATTCC)_n motif ratios may serve as modifiers of SCA10 age at onset rather than repeat length. ATXN10 repeat composition can only be fully resolved with long-read sequencing and makes it a fundamental diagnostic for clinical practice and genetic counseling. These findings underscore the need to adapt long-read sequencing clinical workflows to fully characterize large repeat expansions at the nucleotide level.

The Spinocerebellar Ataxias (SCAs) are a group of autosomal dominant neurodegenerative disorders characterized by progressive cerebellar ataxia, affecting motor coordination. SCAs are reported globally with large geographical and ethnic differences. This systematic review and meta-analysis aimed to update the frequency, and geographic distribution of SCAs in Latin America, including recently identified SCAs like SCA27b. We conducted a systematic search in PubMed, Scopus, LILACS, SciELO and Web of Science databases, including studies published from inception to January 2025. We included 25 studies for the systematic review and 17 studies for the meta-analysis that met the inclusion criteria, representing a total of 5,546 participants across eleven countries. Our meta-analysis revealed that about 61% (95% CI 31–84%) of hereditary ataxias in Latin America were confirmed to have a genetic diagnosis of SCA. The included participants with a known SCA have the following proportions: MJD/SCA3 (34%), SCA2 (30%), SCA10 (9%), SCA7 (9%) and SCA1 (4%). Geographic distributions were notable, MJD/SCA3 in Brazil, SCA2 in Cuba, Argentina and Mexico, SCA10 predominating in Peru, and SCA7 in Venezuela. Recently identified subtypes, like SCA27B and one case of SCA4, were identified in Brazil. In 22 countries there are no published studies on the epidemiology of SCAs. The distribution of SCAs in Latin America reflects the influence of historical migrations, founder effects, and ancestries, emphasizing regional heterogeneity. Our findings underscore the critical need for further epidemiological studies, particularly in understudied countries in the region.