Fast Assays to Detect Interruptions in CTG.CAG Repeat Expansions

2019 ◽  
pp. 11-23
Author(s):  
Stéphanie Tomé ◽  
Geneviève Gourdon
Keyword(s):  
Repeat Expansions

scholarly journals Patients With Extreme Early Onset Juvenile Huntington Disease Can Have Delays in Diagnosis: A Case Report and Literature Review

2021 ◽  
Vol 8 ◽  
pp. 2329048X2110361
Author(s):  
Ashley A. Moeller ◽  
Marcia V. Felker ◽  
Jennifer A. Brault ◽  
Laura C. Duncan ◽  
Rizwan Hamid ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Huntington Disease ◽  
Early Onset ◽  
Trinucleotide Repeat ◽  
Cerebellar Atrophy ◽  
Cag Repeats ◽  
Ataxic Gait ◽  
Repeat Expansions ◽  
Delays In Diagnosis ◽  
Juvenile Huntington Disease

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

scholarly journals REscan: inferring repeat expansions and structural variation in paired-end short read sequencing data

2020 ◽  
Author(s):  
Russell Lewis McLaughlin
Keyword(s):  
Structural Variation ◽  
Sequence Data ◽  
Neurological Diseases ◽  
Repeat Expansion ◽  
Sequencing Data ◽  
Short Read ◽  
Short Read Sequencing ◽  
Repeat Expansions ◽  
Paired End Sequencing

Abstract Motivation Repeat expansions are an important class of genetic variation in neurological diseases. However, the identification of novel repeat expansions using conventional sequencing methods is a challenge due to their typical lengths relative to short sequence reads and difficulty in producing accurate and unique alignments for repetitive sequence. However, this latter property can be harnessed in paired-end sequencing data to infer the possible locations of repeat expansions and other structural variation. Results This article presents REscan, a command-line utility that infers repeat expansion loci from paired-end short read sequencing data by reporting the proportion of reads orientated towards a locus that do not have an adequately mapped mate. A high REscan statistic relative to a population of data suggests a repeat expansion locus for experimental follow-up. This approach is validated using genome sequence data for 259 cases of amyotrophic lateral sclerosis, of which 24 are positive for a large repeat expansion in C9orf72, showing that REscan statistics readily discriminate repeat expansion carriers from non-carriers. Availabilityand implementation C source code at https://github.com/rlmcl/rescan (GNU General Public Licence v3).

The neuropathology associated with repeat expansions in the C9ORF72 gene

2013 ◽  
Vol 127 (3) ◽  
pp. 347-357 ◽  
Author(s):  
Ian R. A. Mackenzie ◽  
Petra Frick ◽  
Manuela Neumann
Keyword(s):  
Repeat Expansions ◽  
C9orf72 Gene

C9ORF72 repeat expansions in Chinese patients with Parkinson’s disease and multiple system atrophy

2016 ◽  
Vol 123 (11) ◽  
pp. 1341-1345 ◽  
Author(s):  
Xueping Chen ◽  
Yongping Chen ◽  
Qianqian Wei ◽  
Ruwei Ou ◽  
Bei Cao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Chinese Patients ◽  
Repeat Expansions

scholarly journals The role of AGG interruptions in fragile X repeat expansions: a twenty-year perspective

2014 ◽  
Vol 5 ◽  
Author(s):  
Gary J. Latham ◽  
Justine Coppinger ◽  
Andrew G. Hadd ◽  
Sarah L. Nolin
Keyword(s):  
Fragile X ◽  
Repeat Expansions ◽  
Agg Interruptions

scholarly journals Screening for novel hexanucleotide repeat expansions at ALS- and FTD-associated loci

2016 ◽  
Vol 2 (3) ◽  
pp. e71 ◽  
Author(s):  
Fang He ◽  
Julie M. Jones ◽  
Claudia Figueroa-Romero ◽  
Dapeng Zhang ◽  
Eva L. Feldman ◽  
...  
Keyword(s):  
Hexanucleotide Repeat ◽  
Repeat Expansions

Questions on NOTCH2NLC Repeat Expansions in Parkinson Disease

2021 ◽  
Author(s):  
Wai Yan Yau ◽  
Henry Houlden ◽  
Jana Vandrovcova
Keyword(s):  
Parkinson Disease ◽  
Repeat Expansions

scholarly journals Screening for C9orf72 repeat expansions in parkinsonian syndromes

2013 ◽  
Vol 34 (4) ◽  
pp. 1311.e3-1311.e4 ◽  
Author(s):  
Tu-Hsueh Yeh ◽  
Szu-Chia Lai ◽  
Yi-Hsin Weng ◽  
Hung-Chou Kuo ◽  
Yah-Huei Wu-Chou ◽  
...  
Keyword(s):  
Parkinsonian Syndromes ◽  
Repeat Expansions

scholarly journals Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1-disease

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011528
Author(s):  
Andreas Traschütz ◽  
Andrea Cortese ◽  
Selina Reich ◽  
Natalia Dominik ◽  
Jennifer Faber ◽  
...  
Keyword(s):  
Natural History ◽  
Late Onset ◽  
Premature Death ◽  
Cross Sectional ◽  
Treatment Trials ◽  
Disease Spectrum ◽  
Phenotypic Spectrum ◽  
Multisystemic Disease ◽  
Repeat Expansions ◽  
Cerebellar Type

Objective:To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of RFC1-repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS).Methods:Multimodal RFC1 repeat screening (PCR, southern blot, whole-exome/genome (WES/WGS)-based approaches) combined with cross-sectional and longitudinal deep-phenotyping in (i) cross-European cohort A (70 families) with ≥2 features of CANVAS and/or ataxia-with-chronic-cough (ACC); and (ii) Turkish cohort B (105 families) with unselected late-onset ataxia.Results:Prevalence of RFC1-disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1-disease was also identified in Western and Eastern Asians, and even by WES. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (=overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea and/or dystonia (11%). Ataxia progression was ∼1.3 SARA points/year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1]), but also included early falls, variable non-linear phases of MSA-C-like progression (SARA 2.5-5.5/year), and premature death. Treatment trials require 330 (1-year-trial) and 132 (2-year-trial) patients in total to detect 50% reduced progression.Conclusions:RFC1-disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes, yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1-treatment trials.Classification of Evidence:This study provides Class II evidence that RFC1-repeat expansions are associated with CANVAS and ACC.

Sign in / Sign up

Export Citation Format

Share Document