Using a roster and haplotyping is useful in risk assessment for persons with intermediate and reduced penetrance alleles in Huntington disease

2001 ◽  
Vol 105 (8) ◽  
pp. 737-744 ◽  
Author(s):  
Anneke Maat-Kievit ◽  
Paula Helderman-van den Enden ◽  
Monique Losekoot ◽  
Peter de Knijff ◽  
Ren� Belfroid ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Huntington Disease ◽  
Reduced Penetrance

scholarly journals Huntington disease reduced penetrance alleles occur at high frequency in the general population

Neurology ◽  
2016 ◽  
Vol 87 (3) ◽  
pp. 282-288 ◽  
Author(s):  
Chris Kay ◽  
Jennifer A. Collins ◽  
Zosia Miedzybrodzka ◽  
Steven J. Madore ◽  
Erynn S. Gordon ◽  
...  
Keyword(s):  
General Population ◽  
Huntington Disease ◽  
High Frequency ◽  
Reduced Penetrance

scholarly journals Frequency of the loss of CAA interruption in the HTT CAG tract and implications for Huntington disease in the reduced penetrance range

2020 ◽  
Vol 22 (12) ◽  
pp. 2108-2113 ◽  
Author(s):  
Hailey Findlay Black ◽  
Galen E. B. Wright ◽  
Jennifer A. Collins ◽  
Nicholas Caron ◽  
Chris Kay ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Reduced Penetrance

scholarly journals Length of uninterrupted CAG repeats, independent of polyglutamine size, results in increased somatic instability and hastened age of onset in Huntington disease

2019 ◽  
Author(s):  
Galen E.B. Wright ◽  
Jennifer A. Collins ◽  
Chris Kay ◽  
Cassandra McDonald ◽  
Egor Dolzhenko ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Autosomal Dominant ◽  
Age Of Onset ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Repeat Polymorphism ◽  
Repeat Instability ◽  
Cag Repeat Expansion ◽  
Genomic Studies ◽  
Reduced Penetrance

ABSTRACTHuntington disease (HD) is an autosomal dominant neurological disorder that is caused by a CAG repeat expansion, translated into polyglutamine, in the huntingtin (HTT) gene. Although the length of this repeat polymorphism is inversely correlated with age of onset (AOO), it does not fully explain the variability in AOO. Genomic studies have provided evidence for the involvement of DNA repair in modifying this trait, potentially through somatic repeat instability. We therefore assessed genetic variants within the 12bp interrupting sequence between the pathogenic CAG repeat and the polymorphic proline (CCG) tract in the HTT gene and identified variants that result in complete loss of interruption (LOI) between the adjacent CAG/CCG repeats. Analysis of multiple HD pedigrees showed that this variant is associated with dramatically earlier AOO and is particularly relevant to HD patients with reduced penetrance alleles. On average AOO of HD is hastened by an average of 25 years in LOI carriers. This finding indicates that the number of uninterrupted CAG repeats is the most significant contributor to AOO of HD and is more impactful than polyglutamine length, which is not altered in these patients. We show that the LOI variant is associated with increases in both somatic and germline repeat instability, demonstrating a potential mechanism for this effect. Screening individuals from the general population (n=2,674 alleles) suggests that the variant occurs only in expanded CAG repeat alleles. Identification of this modifier has important clinical implications for disease management of HD families, especially for those in the reduced penetrance ranges.

scholarly journals Huntington disease: a single-gene degenerative disorder of the striatum

2016 ◽  
Vol 18 (1) ◽  
pp. 91-98 ◽  
Keyword(s):  
Huntington Disease ◽  
Neurodegenerative Disorder ◽  
Normal Population ◽  
Single Gene ◽  
Specific Cell ◽  
Degenerative Disorder ◽  
Reduced Penetrance ◽  
Life Cycle Development ◽  
Eventual Death ◽  
The Brain

Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.

Risk assessment in dentistry

1998 ◽  
Vol 62 (10) ◽  
pp. 756-761 ◽  
Author(s):  
CW Douglass
Keyword(s):  
Risk Assessment
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