Homozygotes for Huntington's disease

  title={Homozygotes for Huntington's disease},
  author={Nancy S Wexler and Anne B. Young and Rudolph E. Tanzi and Helen Travers and Simon Starosta‐Rubinstein and John B. Penney and S. Robert Snodgrass and Ira Shoulson and Fidela Gomez and Mar{\'i}a Antonia Ramos Arroyo and Graciela K. Penchaszadeh and Humberto Moreno and Kerin T. Gibbons and Anne G. Faryniarz and Wendy J. Hobbs and Mary Anne Anderson and Ernesto Bonilla and P. Michael Conneally and James F. Gusella},
Careful comparison of symptomatic individuals with normal controls has revealed the primary biochemical abnormality in many human genetic diseases, particularly recessive disorders1. This strategy has proved less successful for most human disorders which are not recessive, and where a single copy of the aberrant gene has clinically significant effects even though the normal gene product is present. An alternative approach that eliminates the impediment of a normal protein in affected… 
Homozygosity in Huntington's disease: new ethical dilemma caused by molecular diagnosis
The present authors describe a family comparing two affected siblings: one is heterozygotic and the other homozygous for the HD mutation, and confirm that the age and symptoms of onset did not differ significantly between the subjects; however, the disease seemed to have a more severe progression in the heterozygote than in the homozygote.
Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course.
Differences in the disease features between eight homozygotes and 75 heterozygotes for the Huntington disease mutation point to the possibility that the mechanisms underlying age at onset and disease progression in Huntington disease may differ, and suggest that the phenotype and the rate of disease progression may differ.
Dominance and homozygosity.
  • J. Zlotogora
  • Medicine
    American journal of medical genetics
  • 1997
It is confirmed that in most cases homozygotes of dominant disorders are more severely affected than heterozygotes and in some cases molecular analysis allowed an understanding of the mechanisms involved.
Homozygosity in Huntington’s disease
The clinical, neuropsychological, and molecular characterisation of such a patient in comparison to his heterozygous brother is reported, since homozygous carriers of the disease are no more severely affected than heterozygouse carriers.
Huntington's disease
Prenatal exclusion testing offers an alternative method of detecting and terminating at‐risk pregnancies without revealing the genetic status of the at-risk parent.
Clinical manifestations of homozygote allele carriers in Huntington disease
This study provides Class II evidence that age at onset, the motor phenotype and rate of motor decline, and symptoms and signs progression is similar in homozygotes compared to heterozygotes, indicating similar effect on the mutant protein.
A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice.
Analysis of the mutation introduced into the endogenous mouse Hdh gene reveals significant levels of germline instability, which implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain.
Proposed genetic basis of Huntington's disease.
  • C. Laird
  • Biology
    Trends in genetics : TIG
  • 1990
A molecular investigation of true dominance in Huntington’s disease
It is shown that cytoplasmic and nuclear aggregates are formed by constructs comprising part of exon 1 of huntingtin with 41, 51, 66, or 72 CAG repeats, in a rate that correlates with repeat number.
Predictive testing for Huntington's disease with use of a linked DNA marker.
It is concluded that some persons in the early stages of Huntington's disease may seek presymptomatic testing rather than neurologic evaluations.


Deletion of Huntington's disease-linked G8 (D4S10) locus in Wolf–Hirschhorn syndrome
The discovery of this linkage marker G8 raises the possibility of developing a presymptomatic test for Huntington's disease, and of eventually isolating the disease gene based on its map position4.
Homozygosity for autosomal dominant Marfan syndrome.
It is suggested that these two sibs are examples of homozygosity for the Marfan syndrome gene, based on the large number of affected members, the absence of additional consanguinity, manifestation of the syndrome in both parents, and the severity of the disease in the two sIBs.
Dominantly inherited macular degeneration (Best's disease) in a homozygous father with 11 children
The great variations in expressivity of the disease in the 11 children reflected what has been found as a rule in large Swedish families with HMD, and the homozygotic stage did not seem to differ in clinical appearance from the heterozygotic.
Dominance and recessivity in medical genetics.
Huntington disease
The Commission for the Control of Huntington Disease and Its Consequences, established by the Ninety-Fourth United States Congress, recently completed an appraisal of clinical care of the patient and family with Huntington disease.
Camptobrachydactyly: a new autosomal dominant trait with two probable homozygotes.
The syndrome described in one large family in this report presents an apparently unique combination of congenital flexion contractures of the fingers and brachydactyly of the hands and feet with inconstant other features including syndactyyly, polydactYly, septate vagina, and urinary incontinence.
Psychiatric syndromes in Huntington's disease.
Consideration of the array of behavioral disturbances encountered in this pathogenetically unified disorder suggests that a dimensional approach to symptom classification might prove more useful heuristically than present typological methods.
A polymorphic DNA marker genetically linked to Huntington's disease
The chromosomal localization of the Huntington's disease gene is the first step in using recombinant DNA technology to identify the primary genetic defect in this disorder.
Conduct disorder and affective disorder among the offspring of patients with Huntington's disease.
The findings indicated an increased frequency of conduct disorder in disrupted families, most especially in those where the HD parent had an early onset of symptoms and the non-HD parent showed psychiatric disorder.
Huntington's disease in Venezuela
The rate of decline of these untreated patients from Venezuela was similar to that seen in US patients who had received neuroleptic drugs and Juvenile patients declined nearly twice as fast as adult-onset patients.