ResearchPad - 98 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[<i>TGM6</i> L517W is not a pathogenic variant for spinocerebellar ataxia type 35]]> https://www.researchpad.co/article/elastic_article_7785 To investigate the pathogenicity of the TGM6 variant for spinocerebellar ataxia 35 (SCA35), which was previously reported to be caused by pathogenic mutations in the gene TGM6.MethodsNeurologic assessment and brain MRI were performed to provide detailed description of the phenotype. Whole-exome sequencing and dynamic mutation analysis were performed to identify the genotype.ResultsThe proband, presenting with myoclonic epilepsy, cognitive decline, and ataxia, harbored both the TGM6 p.L517W variant and expanded CAG repeats in gene ATN1. Further analysis of the other living family members in this pedigree revealed that the CAG repeat number was expanded in all the patients and within normal range in all the unaffected family members. However, the TGM6 p.L517W variant was absent in 2 affected family members, but present in 3 healthy individuals.ConclusionsThe nonsegregation of the TGM6 variant with phenotype does not support this variant as the disease-causing gene in this pedigree, questioning the pathogenicity of TGM6 in SCA35. ]]> <![CDATA[Consensus-based care recommendations for adults with myotonic dystrophy type 1]]> https://www.researchpad.co/article/5c2d430fd5eed0c484e08c4f

Purpose of review

Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit.

Recent findings

The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations.

Summary

The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments.

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<![CDATA[The complex structure of ATXN2 genetic variation]]> https://www.researchpad.co/article/5c2d4200d5eed0c484e01ca1 ]]> <![CDATA[Homozygous 31 trinucleotide repeats in the SCA2 allele are pathogenic for cerebellar ataxia]]> https://www.researchpad.co/article/5c16ccd1d5eed0c48452370e ]]> <![CDATA[Correlation of clinical and molecular features in spinal bulbar muscular atrophy]]> https://www.researchpad.co/article/5ad6926d463d7e08f36bfec7

Objectives:

To characterize the clinical and genetic features of spinal bulbar muscular atrophy (SBMA), a rare neurodegenerative disorder caused by the expansion of a CAG repeat in the first exon of the androgen receptor gene, in the United Kingdom.

Methods:

We created a national register for SBMA in the United Kingdom and recruited 61 patients between 2005 and 2013. In our cross-sectional study, we assessed, by direct questioning, impairment of activities of daily living (ADL) milestones, functional rating, and subjective disease impact, and performed correlations with both CAG repeat size and degree of somatic mosaicism. Ten patients were deceased, 46 patients participated in the study, and 5 declined.

Results:

Subjects had an average age at onset of 43.4 years, and weakness onset most frequently occurred in the lower limbs (87%). Impaired mobility was the most frequently reported problem by patients, followed by bulbar dysfunction. Age distribution of the impairment of ADL milestones showed remarkable overlap with a Japanese study. We have identified a significant correlation between the number of CAG repeats and both age at onset and ADL milestones. Somatic mosaicism also showed a correlation with CAG expansion size and age at onset.

Conclusions:

Clinical features in SBMA show a substantial overlap when comparing populations with different genetic backgrounds. This finding has major implications, because multicenter trials will be necessary to obtain sufficient power in future clinical trials. Clinical-genetic correlations are strong in SBMA and should inform any clinical research strategy in this condition.

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