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.
Humans ; Spinocerebellar Ataxias/pathology* ; Ataxia/genetics* ; Muscle Spasticity/genetics*

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.
Female ; Humans ; Heat-Shock Proteins/genetics* ; Muscle Spasticity/genetics* ; Mutation ; Spinocerebellar Ataxias/pathology* ; Child, Preschool

Spinocerebellar ataxia type 2 (SCA2) is a rare autosomal dominant progressive degenerative disease of the nervous system, which is characterized by a progressive cerebellar syndrome associated with saccadic eye scan, peripheral neuropathy, cognitive disorders, and other multisystem features. The gene predisposing to SCA2 has been mapped, which encodes the ataxin 2 protein. A CAG repeat expansion in the coding region of ATXN2 gene can cause extension of polyglutamine chain in the protein. This paper reviews recent progress made in the research on SCA2 in regard to its clinical features, pathology, etiology, pathogenesis and treatment.
Animals ; Ataxin-2 ; genetics ; Humans ; Spinocerebellar Ataxias ; etiology ; genetics ; pathology ; therapy

Quality control for genetic analysis has become more important with a drastic increase in testing volume and clinical demands. The molecular diagnostics division of the Korean Association of Quality Assurance for Clinical Laboratory conducted two trials in 2017 on the basis of molecular diagnostics surveys, involving 53 laboratories. The molecular diagnostics surveys included 37 tests: gene rearrangement tests for leukemia (BCR-ABL1, PML-RARA, AML1-ETO, and TEL-AML1), genetic tests for Janus kinase 2, FMS-like tyrosine kinase 3-internal tandem duplication, FMS-like tyrosine kinase 3-tyrosine kinase domain, nucleophosmin, cancer-associated genes (KRAS, EGFR, KIT, and BRAF), hereditary breast and ovarian cancer genes (BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Wilson disease (ATP7B), achondroplasia (FGFR3), hearing loss and deafness (GJB2), Avellino (TGFBI), multiple endocrine neoplasia 2 (RET), Huntington disease, spinocerebellar ataxia, spinal and bulbar muscular atrophy, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, myoclonic epilepsy ragged red fibre, Leber hereditary optic neuropathy, Prader-raderd Angelman syndrome, Duchenne muscular dystrophy, spinal muscular atrophy, fragile X syndrome, apolipoprotein E genotyping, methylenetetrahydrofolate reductase genotyping, and ABO genotyping. Molecular genetic surveys revealed excellent results for most participants. The external quality assessment program for genetic analysis in 2017 proved useful for continuous education and the evaluation of quality improvement.
Achondroplasia ; Acidosis, Lactic ; Angelman Syndrome ; Apolipoproteins ; Brain Diseases ; Breast ; Deafness ; Education ; Epilepsies, Myoclonic ; Fragile X Syndrome ; Gene Rearrangement ; Hearing Loss ; Hepatolenticular Degeneration ; Huntington Disease ; Janus Kinase 2 ; Korea* ; Laboratory Proficiency Testing ; Leukemia ; Li-Fraumeni Syndrome ; Methylenetetrahydrofolate Reductase (NADPH2) ; Molecular Biology ; Multiple Endocrine Neoplasia ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic ; Muscular Dystrophy, Duchenne ; Optic Atrophy, Hereditary, Leber ; Ovarian Neoplasms ; Pathology, Molecular* ; Phosphotransferases ; Quality Control ; Quality Improvement ; Spinocerebellar Ataxias ; Vascular Endothelial Growth Factor Receptor-1

Non-coding expansion spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases characterized by "CTA/CTG", "ATTCT", "TGGAA" expansion in non-coding region of the causative gene. Until now, 5 subtypes including SCA8, SCA10, SCA12, SCA31 and SCA36 have been mapped. Recently, the causative mutation for SCA36, namely intronic hexanucleotide GGCCTG expansion in NOP56 gene, has been identified in Japanese and Spanish pedigrees in succession. Compared with other subtypes of SCAs, there are certain distinctive characteristics for SCA36. The clinical and genetic features of SCA36 are reviewed in this paper.
Base Sequence ; Biomedical Research ; methods ; trends ; Chromosome Mapping ; Chromosomes, Human, Pair 20 ; genetics ; DNA Repeat Expansion ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Nuclear Proteins ; genetics ; Oligonucleotides ; genetics ; Spinocerebellar Ataxias ; genetics ; pathology

BACKGROUNDSpinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs.

METHODSIn this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado-Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.

RESULTSWe found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.

CONCLUSIONSCollectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.

Adult ; DNA Repeat Expansion ; genetics ; Female ; Humans ; Machado-Joseph Disease ; genetics ; pathology ; Male ; Mutation ; genetics ; Spinocerebellar Ataxias ; genetics ; pathology ; Trinucleotide Repeat Expansion ; genetics

Hereditary spinocerebellar ataxia type 17 (SCA17) is an autosomal dominantly inherited progressive degenerative disease of the nervous system. Also known as Huntington's disease-like 4(HDL4), SCA17 mainly features ataxia, muscle dystonia and psychiatric symptoms. The gene predisposing to SCA17 has been mapped and cloned, which encodes a TATA-binding protein (TBP). A CAG repeat expansion in the coding region of TBP gene can cause polyglutamine chain extension in the protein. This paper reviews recent progress in the research on SCA17 in regard to its clinical, etiology, pathology and pathogenesis.
Animals ; Humans ; Huntington Disease ; genetics ; pathology ; Spinocerebellar Ataxias ; genetics ; pathology ; TATA-Box Binding Protein ; genetics ; Trinucleotide Repeat Expansion

A 60-yr-old man developed progressive gait disturbance and limb ataxia at the age of 52. Family history was absent for neurological disorders. Examinations showed pure cerebellar syndrome. There was no retinal degeneration for 7 yr. A brain MRI done at the age of 56 showed atrophy of the cerebellar hemispheres and vermis. Genetic test confirmed the spinocerebellar ataxia type 7 with CAG repeat number of 42.
Brain/pathology ; Humans ; Korea ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retinal Degeneration/genetics/*pathology ; Spinocerebellar Ataxias/genetics/*pathology ; Trinucleotide Repeat Expansion

Spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2) and familial hemiplegic migraine (FHM) have been known as allelic disorders, which are caused by the alteration of the alpha1A voltage-dependent calcium channel subunit. Expansions of the CAG repeat in the CACNA1A gene on the short arm of the chromosome 19 induce SCA6, and point mutations in the same gene are responsible for EA2 and FHM. In recent studies, both SCA6 and EA2 have been concurrently found in families with 26 CAG repeats without previously reported point mutations either in coding sequences or in intron-exon junctions. We describe a Korean family with CAG26 repeats in the CACNA1A gene. Some of the affected family members had progressive ataxia typical of SCA6 whereas others had episodic vertigo responsive to acetazolamide typical of EA2. Our family support that SCA6 and EA2 are allelic disorders with a high phenotypic variability.
Adolescence ; Adult ; Aged ; Calcium Channels/genetics ; Case Report ; Child ; *Family Health ; Female ; Human ; Korea ; Magnetic Resonance Imaging ; Male ; Middle Age ; Pedigree ; Phenotype ; Spinocerebellar Ataxias/*genetics/*pathology/radionuclide imaging ; Tomography, Emission-Computed, Single-Photon

BACKGROUND: Spinocerebellar ataxia 6 (SCA6) is an autosomal dominant spinocerebellar degeneration and caused by the expansion of the polymorphic CAG repeat in the human alpha 1A voltage-dependent calcium channel subunit gene. In this study, we report the clinical and molecular genetic characteristics of SCA6 in 2 Korean families. We further describe that SCA6 and Episodic ataxia type 2 are simultaneously developed in same family showing no intergenerational changes of CAG repeat numbers. METHODS: Seventeen members of one family and nine of the other received detailed neurological examination and history taking at least one occasion. After the screening test, molecular diagnostic test by using Zhuchenko's method were performed in 13 patients in one family and 3 in the other, respectively. RESULTS: Normal range of CAG repeat in 92 normal individuals was 8 to 17. In this study, the numbers of CAG repeat in one family was 26 and in another was 23. There were no intergenerational differences in the numbers of CAG repeat. Despite the same number of CAG repeat, the clinical anticipation were found. Only one showed episodic ataxia clinically. CONCLUSIONS: Comparing with other types of SCA, the SCA6 had several remarkable characteristics: 1) very small CAG expansions (21-27 repeats) lead to clinical symptoms and the repeat numbers are relatively stable, 2) clinical anticipation is observed despite the relatively stable repeat on intergenerational transmission. The finidngs that an EA2 and a SCA6 exist in a same family may be suggest that two disease are the same disorder with a high phenotypic variablity.
Ataxia ; Calcium Channels ; Humans ; Mass Screening ; Molecular Biology ; Neurologic Examination ; Pathology, Molecular ; Reference Values ; Spinocerebellar Ataxias* ; Spinocerebellar Degenerations