Spinocerebellar ataxias: An example of the challenges associated with genetic databases for dynamic mutations

2012 ◽  
Vol 33 (9) ◽  
pp. 1359-1365 ◽  
Author(s):  
Joanne E. Martindale ◽  
Sara Seneca ◽  
Stefan Wieczorek ◽  
Jorge Sequeiros
Keyword(s):  
Spinocerebellar Ataxias ◽  
Dynamic Mutations

scholarly journals The occurrence of spinocerebellar ataxias caused by dynamic mutations in Polish patients

2010 ◽  
Vol 44 (3) ◽  
pp. 238-245 ◽  
Author(s):  
Anna Sułek-Piątkowska ◽  
Elżbieta Zdzienicka ◽  
Maria Rakowicz ◽  
Wioletta Krysa ◽  
Marta Rajkiewicz ◽  
...  
Keyword(s):  
Spinocerebellar Ataxias ◽  
Dynamic Mutations

scholarly journals The dynamic mutation investigation and whole exome sequencing in a cohort of Chinese autosomal dominant cerebellar ataxia patients

2020 ◽  
Author(s):  
Fang Peng ◽  
Yue Zhang ◽  
Xin-Yue Zhou ◽  
Shuai-Qi Huang ◽  
Chen Chen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Exome Sequencing ◽  
Cerebellar Ataxia ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Autosomal Dominant Cerebellar Ataxia ◽  
Spinocerebellar Ataxias ◽  
Dynamic Mutation ◽  
Whole Exome ◽  
Dynamic Mutations

Abstract Background Spinocerebellar ataxias (SCAs) are the autosomal dominant cerebellar ataxia (ADCA) with great clinical and genetic heterogeneity. Genetic testing will contribute to the final diagnosis. Methods A total of 204 Chinese ADCA patients were recruited and 190 had genetic testing. Dynamic mutations of SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) were screened firstly. For the patients with negative results, the dynamic mutations of HTT of Huntington Disease (HD), SCA31, 36 and even the whole exome sequencing (WES) were further performed. We investigated the genetic results and clinical characteristics retrospectively. Results Among these 190 index cases, 177(93.16%) were identified SCA dynamic mutations. SCA3 was the commonest, accounting for 70.06%, followed by SCA1 (9.6%), 2 (9.05%), 12 (3.39%), 6 (2.26%), DRPLA (2.26%), 7(1.13%), 8 (1.13%) and 17(0.56%). One patient carried a compound dynamic mutation of SCA6 and SCA17 (SCA6/17). No SCA10 or SCA36 was found. Among the remaining 13 patients, three were diagnosed with HD (1.58%) and one with Episodic Ataxia 2 (EA2). WES did reveal several variants with uncertain significance (VUS) in the remaining nine patients, but failed to detect causative mutations. Conclusion We illustrated the approach and challenge of genetic testing in Chinese ADCA patients. Dynamic mutations of SCAs should be screened firstly. When the results were negative, dynamic mutation of HTT would better be screened consequently. In early-onset ADCA patients, WES might be effective to identify causative mutations, but in adult-onset cases, WES might be less effective.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

scholarly journals Idiopathic Infertility as a Feature of Genome Instability

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 628
Author(s):  
Agrita Puzuka ◽  
Baiba Alksere ◽  
Linda Gailite ◽  
Juris Erenpreiss
Keyword(s):  
Life Expectancy ◽  
Male Infertility ◽  
Genome Instability ◽  
Repair System ◽  
Environmental Aspects ◽  
Strand Breaks ◽  
Testicular Dysfunction ◽  
Infertile Men ◽  
Dna Strand ◽  
Dynamic Mutations

Genome instability may play a role in severe cases of male infertility, with disrupted spermatogenesis being just one manifestation of decreased general health and increased morbidity. Here, we review the data on the association of male infertility with genetic, epigenetic, and environmental alterations, the causes and consequences, and the methods for assessment of genome instability. Male infertility research has provided evidence that spermatogenic defects are often not limited to testicular dysfunction. An increased incidence of urogenital disorders and several types of cancer, as well as overall reduced health (manifested by decreased life expectancy and increased morbidity) have been reported in infertile men. The pathophysiological link between decreased life expectancy and male infertility supports the notion of male infertility being a systemic rather than an isolated condition. It is driven by the accumulation of DNA strand breaks and premature cellular senescence. We have presented extensive data supporting the notion that genome instability can lead to severe male infertility termed “idiopathic oligo-astheno-teratozoospermia.” We have detailed that genome instability in men with oligo-astheno-teratozoospermia (OAT) might depend on several genetic and epigenetic factors such as chromosomal heterogeneity, aneuploidy, micronucleation, dynamic mutations, RT, PIWI/piRNA regulatory pathway, pathogenic allelic variants in repair system genes, DNA methylation, environmental aspects, and lifestyle factors.

scholarly journals Nonmotor symptoms in spinocerebellar ataxias (SCAs)

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Adriana Moro ◽  
Mariana Moscovich ◽  
Marina Farah ◽  
Carlos Henrique F. Camargo ◽  
Hélio A. G. Teive ◽  
...  
Keyword(s):  
Spinocerebellar Ataxias ◽  
Nonmotor Symptoms

Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin

2009 ◽  
Vol 454 (2) ◽  
pp. 157-160 ◽  
Author(s):  
Luis Velázquez Pérez ◽  
Gilberto Sánchez Cruz ◽  
Nieves Santos Falcón ◽  
Luis Enrique Almaguer Mederos ◽  
Karel Escalona Batallan ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Founder Effect ◽  
Spinocerebellar Ataxias
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