Unstable familial transmissions of Huntington disease alleles with 27-35 CAG repeats (intermediate alleles)

2009 ◽  
Vol 9999B ◽  
pp. n/a-n/a ◽  
Author(s):  
A. Semaka ◽  
J.A. Collins ◽  
M.R. Hayden
Keyword(s):  
Huntington Disease ◽  
Cag Repeats ◽  
Intermediate Alleles

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 Incidence of Huntington disease in a northeastern Spanish region: a 13-year retrospective study at tertiary care centre

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Paula Sienes Bailo ◽  
Raquel Lahoz ◽  
Juan Pelegrín Sánchez Marín ◽  
Silvia Izquierdo Álvarez
Keyword(s):  
Retrospective Study ◽  
Huntington Disease ◽  
Tertiary Care ◽  
Genetic Diagnosis ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Incomplete Penetrance ◽  
Predictive Test ◽  
Incident Cases

Abstract Background Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases. Methods Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100,000 inhabitants per year during the period 2007–2019 in Aragon (Spain). Results 50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (72.1%) were HD negative (CAG repeat length < 36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 0.648 per 100,000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 9 and the most common CAG length among HD negative individuals was 16. Conclusions Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

scholarly journals Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Dorra Hmida-Ben Brahim ◽  
Marwa Chourabi ◽  
Sana Ben Amor ◽  
Imed Harrabi ◽  
Saoussen Trabelsi ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Age At Onset ◽  
Specific Effect ◽  
Modifier Genes ◽  
Cag Repeats ◽  
Causative Mutation ◽  
Cag Expansion ◽  
Tunisian Patients

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO) of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.

scholarly journals A Case of Previously Unsuspected Huntington Disease Diagnosed at Autopsy

2017 ◽  
Vol 7 (1) ◽  
pp. 136-144
Author(s):  
Catherine R. Miller ◽  
Nobby C. Mambo ◽  
Jianli Dong ◽  
Gerald A. Campbell
Keyword(s):  
Genetic Testing ◽  
Huntington Disease ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Case Reports ◽  
Neuronal Loss ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Psychiatric Disturbances ◽  
Personality Changes

Huntington disease (HD) is a neurodegenerative disorder with a worldwide prevalence of four to ten per 100 000. It is characterized by choreiform movements, behavioral/psychiatric disturbances, and eventual cognitive decline. Symptoms usually present between 30 and 50 years of age and the diagnosis is based on the combination of clinical symptoms, family history, and genetic testing. A variation of HD, juvenile Huntington disease (JHD), presents earlier, with more severe symptoms and with a worse prognosis. Symptoms are different in JHD, with personality changes and learning difficulties being the predominant presenting features. Seizures are common in JHD, and chorea is uncommon; movement disorders at presentation of JHD are predominantly nonchoreiform. The inheritance pattern for both HD and JHD is autosomal dominant and the disease is caused by an elongation of the CAG repeat in the huntingtin gene. There are many published case reports of Huntington disease that were confirmed at autopsy, but to our knowledge, there are no reports in the literature where the diagnosis of Huntington disease was first made at autopsy. We present a case of a 28-year-old African-American male who was in a state of neglect due to a lifetime of abuse, cognitive difficulties, and seizures, whose cause of death was pneumonia. The gross autopsy findings included bilateral caudate nucleus atrophy and lateral ventricular dilation. Microscopically, severe bilateral neuronal loss and gliosis of the caudate and putamen nuclei were seen. Genetic testing for the number of CAG repeats confirmed the diagnosis and was consistent with JHD.

scholarly journals FACS-array–based cell purification yields a specific transcriptome of striatal medium spiny neurons in a murine Huntington disease model

2020 ◽  
Vol 295 (29) ◽  
pp. 9768-9785 ◽  
Author(s):  
Haruko Miyazaki ◽  
Tomoyuki Yamanaka ◽  
Fumitaka Oyama ◽  
Yoshihiro Kino ◽  
Masaru Kurosawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Huntington Disease ◽  
Fluorescent Protein ◽  
Neurodegenerative Disorder ◽  
Disease Model ◽  
Medium Spiny Neuron ◽  
Cag Repeats ◽  
Specific Gene ◽  
Protein Marker ◽  
Gene Sets

Huntington disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the Huntingtin gene. Results from previous studies have suggested that transcriptional dysregulation is one of the key mechanisms underlying striatal medium spiny neuron (MSN) degeneration in HD. However, some of the critical genes involved in HD etiology or pathology could be masked in a common expression profiling assay because of contamination with non-MSN cells. To gain insight into the MSN-specific gene expression changes in presymptomatic R6/2 mice, a common HD mouse model, here we used a transgenic fluorescent protein marker of MSNs for purification via FACS before profiling gene expression with gene microarrays and compared the results of this “FACS-array” with those obtained with homogenized striatal samples (STR-array). We identified hundreds of differentially expressed genes (DEGs) and enhanced detection of MSN-specific DEGs by comparing the results of the FACS-array with those of the STR-array. The gene sets obtained included genes ubiquitously expressed in both MSNs and non-MSN cells of the brain and associated with transcriptional regulation and DNA damage responses. We proposed that the comparative gene expression approach using the FACS-array may be useful for uncovering the gene cascades affected in MSNs during HD pathogenesis.

scholarly journals Genotyping single nucleotide polymorphisms for allele-selective therapy in Huntington disease

2020 ◽  
Vol 6 (3) ◽  
pp. e430 ◽  
Author(s):  
Daniel O. Claassen ◽  
Jody Corey-Bloom ◽  
E. Ray Dorsey ◽  
Mary Edmondson ◽  
Sandra K. Kostyk ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Huntington Disease ◽  
Prospective Observational Study ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cag Repeat Expansion ◽  
Long Read ◽  
Selective Therapy

BackgroundThe huntingtin gene (HTT) pathogenic cytosine-adenine-guanine (CAG) repeat expansion responsible for Huntington disease (HD) is phased with single nucleotide polymorphisms (SNPs), providing targets for allele-selective treatments.ObjectiveThis prospective observational study defined the frequency at which rs362307 (SNP1) or rs362331 (SNP2) was found on the same allele with pathogenic CAG expansions.MethodsAcross 7 US sites, 202 individuals with HD provided blood samples that were processed centrally to determine the number and size of CAG repeats, presence and heterozygosity of SNPs, and whether SNPs were present on the mutant HTT allele using long-read sequencing and phasing.ResultsHeterozygosity of SNP1 and/or SNP2 was identified in 146 (72%) individuals. The 2 polymorphisms were associated only with the mHTT allele in 61% (95% high density interval: 55%, 67%) of individuals.ConclusionsThese results are consistent with previous reports and demonstrate the feasibility of genotyping, phasing, and targeting of HTT SNPs for personalized treatment of HD.

Patient-reported impact of symptoms in Huntington disease

Neurology ◽  
2020 ◽  
Vol 94 (19) ◽  
pp. e2045-e2053
Author(s):  
Alistair M. Glidden ◽  
Elizabeth A. Luebbe ◽  
Molly J. Elson ◽  
Steven B. Goldenthal ◽  
Christopher W. Snyder ◽  
...  
Keyword(s):  
Functional Capacity ◽  
Huntington Disease ◽  
Disease Burden ◽  
Cag Repeats ◽  
Relative Importance ◽  
Cross Sectional ◽  
Cross Correlation Analysis ◽  
Patient Reported ◽  
Emotional Issues ◽  
Total Functional Capacity

ObjectiveTo determine the frequency and relative importance of symptoms experienced by adults with Huntington disease (HD) and to identify factors associated with a higher disease burden.MethodsWe performed 40 qualitative interviews (n = 20 with HD, n = 20 caregivers) and analyzed 2,082 quotes regarding the symptomatic burden of HD. We subsequently performed a cross-sectional study with 389 participants (n = 156 with HD [60 of whom were prodromal], n = 233 caregivers) to assess the prevalence and relative importance (scale 0–4) of 216 symptoms and 15 symptomatic themes in HD. Cross-correlation analysis was performed based on sex, disease duration, age, number of CAG repeats, disease burden, Total Functional Capacity score, employment status, disease status, and ambulatory status.ResultsThe symptomatic themes with the highest prevalence in HD were emotional issues (83.0%), fatigue (82.5%), and difficulty thinking (77.0%). The symptomatic themes with the highest relative importance to participants were difficulty thinking (1.91), impaired sleep or daytime sleepiness (1.90), and emotional issues (1.81). High Total Functional Capacity scores, being employed, and having prodromal HD were associated with a lower prevalence of symptomatic themes. Despite reporting no clinical features of the disease, prodromal individuals demonstrated high rates of emotional issues (71.2%) and fatigue (69.5%). There was concordance between the prevalence of symptoms reported by manifest individuals and caregivers.ConclusionsMany symptomatic themes affect the lives of those with HD. These themes have a variable level of importance to the HD population and are identified both by those with HD and by their caregivers.

NONAGENARIANS WITH HUNTINGTON DISEASE (HD) HAVE LOW CAG REPEATS

1999 ◽  
Vol 58 (5) ◽  
pp. 549 ◽  
Author(s):  
D Karluk ◽  
R H Myers ◽  
M DiFiglia ◽  
J F Gusella ◽  
M E MacDonald ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Cag Repeats
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