Genetic analysis of a child with Charlevoix-Saguenay spastic ataxia due to variant of SACS gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS).@*METHODS@#Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases.@*CONCLUSION@#The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.

Research advance on the pathogenesis of autosomal recessive spastic ataxia of Charlevoix-Saguenay / 中华医学遗传学杂志

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare and early-onset neurodegenerative disease caused by variants of the SACS gene which maps to chromosome 13q11 and encodes sacsin protein. Sacsin is highly expressed in large motor neurons, in particular cerebellar Purkinje cells. This article has provided a review for the structure and function of sacsin protein and the mechanisms underlying abnormalities of sacsin in ARSACS disease.

Abordagem fisioterapêutica da ataxia espinocerebelar: uma revisão sistemática / Physical therapy approach to spinocerebellar ataxia: a systematic review / El abordaje fisioterapéutico de la ataxia espinocerebelosa: una revisión sistemática

A ataxia espinocerebelar (SCA) é uma afecção hereditária que cursa com a degeneração progressiva do cerebelo e suas vias, causando alterações do equilíbrio e de outras funções. O efeito das abordagens da fisioterapia no tratamento da SCA e a qualidade metodológica desses estudos foram analisados. Foi investigado ainda se os benefícios alcançados com o tratamento são retidos. As intervenções encontradas incluem treino do equilíbrio, marcha e coordenação; fortalecimento; caneleiras nos membros durante exercícios e aplicação de estimulação magnética transcraniana. A retenção das melhoras obtidas com o tratamento foi relacionada ao grau de evolução da SCA e à continuidade da prática de exercícios. Porém, novos estudos com maior rigor científico são necessários para eleger as abordagens mais adequadas para o tratamento de portadores de SCA...

The spinocerebellar ataxia (SCA) is an inherited disorder that leads to progressive degeneration of the cerebellum and its pathways with impairments of balance and other functions. Physical therapy studies for SCA treatment and their methodological quality were examined. We also investigated if the benefits achieved with treatment can be retained. The interventions identified included balance, gait and coordination training; strengthening; weights around the limbs during exercise and transcranial magnetic stimulation. The long-term improvements were related to the degree of SCA evolution and the continuity of exercise practice. Nevertheless, further studies with higher scientific accuracy are necessary to elect the best physical therapy approaches for SCA patients...

La ataxia espinocerebelosa (SCA) es una afección hereditaria que cursa con la degeneración progresiva del cerebelo y de sus vías, lo que causa alteraciones del equilibrio y de otras funciones. El resultado de los abordajes de la fisioterapia en el tratamiento de la SCA y la cualidad metodológica de estos estudios fueron analizados. Se investigó si los beneficios alcanzados con el tratamiento fueron retenidos. Las intervenciones encontradas incluyen entrenamiento del equilibrio, marcha y coordinación; fortalecimiento; canilleras en los miembros durante ejercicios y aplicación de la estimulación magnética transcraneana. La retención de las mejorías obtenidas con el tratamiento fue relacionada al grado de evolución de la SCA y a la continuidad de la práctica de ejercicios. Aunque nuevos estudios con mayor carácter científico son necesarios para elegir los abordajes más adecuados para el tratamiento de los portadores de la SCA...

Ataxia espinocerebelosa 7: Investigación clínica y genética en una familia argentina / Spinocerebellar ataxia 7: Clinical and genetic investigation in an Argentine family

Las ataxias espino cerebelosas (AEC), constituyen un grupo de trastornos hereditarios neurodegenerativos de herencia autosómica dominante. Se caracterizan principalmente por la presencia clínica de ataxia cerebelosa asociada a oftalmoplejía, disartria, signos piramidales o extrapiramidales y pérdida de la sensibilidad profunda. La AEC 7 pertenece al grupo de las ataxias espinocerebelosas en la cual el trastorno es consecuencia de la expansión del triplete CAG localizado en el cromosoma 3 p12-p21. La característica clínica de dicha ataxia es la pérdida de la agudeza visual y posterior ceguera. Presentamos tres individuos de una familia con ataxia cerebelosa, pérdida de la agudeza visual y otros signos neurológicos. El diagnóstico fue confirmado por medio del análisis genético en el cual se observó la anormalidad característica de la AEC 7. Este es el primer caso de AEC 7 en Argentina confirmado por estudio genético. En la revisión de la literatura (hasta enero 2006) se hallaron sólo dos familias notificadas en América Latina. El objetivo del trabajo es el de enfocar la atención en el diagnóstico de esta enfermedad degenerativa en pacientes que se presentan con ataxia cerebelosa progresiva asociada con disminución de la agudeza visual e historia familiar positiva.

Spino cerebellar ataxia (SCA) are a complex group of hereditary neurodegenerative disturbances of autosomal dominant pattern. They are largely characterized by the clinical presence of cerebellar ataxia related to ophtalmoplegia, dysarthria, pyramidal and extra-pyramidal signs and loss of deep sensitivity. SCA 7 belongs to the SCA group in which the disturbance is a result of the expansion of CAG triplet repetition located in the 3p12-p21 chromosome. The characteristic clinical feature of SCA7 is the loss of visual acuity and blindness. We present here three cases of ataxia, from the same family, with loss of visual acuity and other neurological disorders. The diagnosis was confirmed by a genetic analysis of the index case in whom the characteristic genetic abnormality of SCA7 was discovered. To our knowledge, this is the first case of SCA7 confirmed by genetic study in Argentina. Only two other reports on family cases were found in a review of the literature of Latin America up to January 2006. The purpose of our report is to draw attention to the diagnosis of this degenerative disease in patients with progressive cerebellar ataxia associated with loss of visual acuity symptoms, where a positive family history is found.