Correlations between molecular and clinical data in Huntington's disease and implications for predictive testing

1995 ◽  
Vol 7 (1) ◽  
pp. 7-12
Author(s):  
S. Claes ◽  
M. Decruyenaere ◽  
R. Dom ◽  
M. Malfroid ◽  
G. Evers-Kiebooms ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Data ◽  
Human Genetics ◽  
Age At Onset ◽  
Genetic Defect ◽  
Biological Marker ◽  
Predictive Testing ◽  
Testing Procedure ◽  
Autosomal Dominant Disorder

SummaryHuntington's disease (HD) is an autosomal dominant disorder of the central nervous system, characterised by neurological, cognitive and psychiatric pathology. Recently the causative genetic defect was discovered. We present a retrospective study of 59 HD patients, investigating correlations between molecular and clinical data.The correlation between CAG-repeatlength and age at onset is confirmed. No correlations between this biological marker and other clinical features are found (symptoms at onset, mode of progression of the disease).The consequences of these findings for predictive testing are discussed. Furthermore, a short overview of the predictive testing procedure in the Center for Human Genetics in Leuven (Belgium) is given.

scholarly journals The Contribution of Somatic Expansion of the CAG Repeat to Symptomatic Development in Huntington’s Disease: A Historical Perspective

2021 ◽  
Vol 10 (1) ◽  
pp. 7-33
Author(s):  
Darren G. Monckton
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Human Genetics ◽  
Age At Onset ◽  
Cag Repeat ◽  
Model Systems ◽  
Causative Mutation ◽  
Inverse Association ◽  
Independent Manner ◽  
Dna Mismatch

The discovery in the early 1990s of the expansion of unstable simple sequence repeats as the causative mutation for a number of inherited human disorders, including Huntington’s disease (HD), opened up a new era of human genetics and provided explanations for some old problems. In particular, an inverse association between the number of repeats inherited and age at onset, and unprecedented levels of germline instability, biased toward further expansion, provided an explanation for the wide symptomatic variability and anticipation observed in HD and many of these disorders. The repeats were also revealed to be somatically unstable in a process that is expansion-biased, age-dependent and tissue-specific, features that are now increasingly recognised as contributory to the age-dependence, progressive nature and tissue specificity of the symptoms of HD, and at least some related disorders. With much of the data deriving from affected individuals, and model systems, somatic expansions have been revealed to arise in a cell division-independent manner in critical target tissues via a mechanism involving key components of the DNA mismatch repair pathway. These insights have opened new approaches to thinking about how the disease could be treated by suppressing somatic expansion and revealed novel protein targets for intervention. Exciting times lie ahead in turning these insights into novel therapies for HD and related disorders.

scholarly journals Huntington’s Disease Pathogenesis: Two Sequential Components

2021 ◽  
Vol 10 (1) ◽  
pp. 35-51 ◽  
Author(s):  
Eun Pyo Hong ◽  
Marcy E. MacDonald ◽  
Vanessa C. Wheeler ◽  
Lesley Jones ◽  
Peter Holmans ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Human Genetics ◽  
Neurodegenerative Disorder ◽  
Genetic Defect ◽  
Genome Project ◽  
Dna Polymorphisms ◽  
Genetic Linkage Analysis ◽  
Abnormal Movements ◽  
Hd Gene

Historically, Huntington’s disease (HD; OMIM #143100) has played an important role in the enormous advances in human genetics seen over the past four decades. This familial neurodegenerative disorder involves variable onset followed by consistent worsening of characteristic abnormal movements along with cognitive decline and psychiatric disturbances. HD was the first autosomal disease for which the genetic defect was assigned to a position on the human chromosomes using only genetic linkage analysis with common DNA polymorphisms. This discovery set off a multitude of similar studies in other diseases, while the HD gene, later renamed HTT, and its vicinity in chromosome 4p16.3 then acted as a proving ground for development of technologies to clone and sequence genes based upon their genomic location, with the growing momentum of such advances fueling the Human Genome Project. The identification of the HD gene has not yet led to an effective treatment, but continued human genetic analysis of genotype-phenotype relationships in large HD subject populations, first at the HTT locus and subsequently genome-wide, has provided insights into pathogenesis that divide the course of the disease into two sequential, mechanistically distinct components.

“organic Personality Disorder” as Part of Early Neuropsychiatric Manifestations in Huntington’s Disease - a Case Report

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Maia
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Psychiatric Symptoms ◽  
Age Of Onset ◽  
Neuropsychiatric Symptoms ◽  
Personality Change ◽  
Psychotic Symptoms ◽  
Autosomal Dominant Disorder ◽  
Neuropsychiatric Manifestations ◽  
Psychiatric Manifestations

Huntington's Disease (HD) is an inherited autosomal dominant disorder characterized by motor, cognitive and psychiatric symptomatology, being considered a paradigmatic neuropsychiatric disorder that includes all three components of the "Triadic Syndromes": dyskinesia, dementia and depression.Firstly described in 1872 as an "Hereditary Chorea" by George Huntington only in 1993 was its responsible gene identified. A person who inherits the HD gene will sooner or later develop the disease. the age of onset, early signs and rate of disease progression vary greatly from person to person.Neuropsychiatric symptoms are an integral part of HD and have been considered the earliest markers of the disease, presenting sometimes more than 10 years before a formal diagnosis is done. Patients may experience dysphoria, mood swings, agitation, irritability, hostile outbursts, psychotic symptoms and deep bouts of depression with suicidal ideation. Personality change is reported in 48% of the cases, with the paranoid subtype being described as the most prevalent. the clinical case presented illustrates a case of HD which started with insidious psychiatric symptoms and an important personality change.Despite a wide number of medications being prescribed to help control emotional, movement and behaviour problems, there is still no treatment to stop or reverse the course of the disease. Furthermore, psychiatric manifestations are often amenable to treatment, and relief of these symptoms may provide significant improvement in patient's and caregivers quality of life.A greater awarness of psychiatric manifestations of HD is essential to an earlier diagnosis and an optimized therapeutic approach.

Reproductive history after predictive testing for Huntington’s disease

2010 ◽  
pp. 45-68
Author(s):  
Gerry Evers-Kiebooms ◽  
Kurt Nys ◽  
Peter S Harper ◽  
Moniek W Zoeteweij ◽  
Alexandra Dürr ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Predictive Testing ◽  
Reproductive History

Imaging and Clinical Data on Swallowing Function of Individuals with Huntington’s Disease and Dysphagia

2020 ◽  
Vol 9 (2) ◽  
pp. 163-171
Author(s):  
Megan Keage ◽  
Shira Baum ◽  
Lisa Pointon ◽  
Jane Lau ◽  
Jacinta Berndt ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Data ◽  
Swallowing Function
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