Diagnostic genetic testing for Huntington's disease

Craufurd, David; MacLeod, Rhona; Frontali, Marina; Quarrell, Oliver; Bijlsma, Emilia K.; Davis, Mary B.; Hjermind, Lena E.; Lahiri, Nayanjot; Mandich, Paola; Martínez, Asunción; Tibben, Aad; Roos, Raymund A.C.

doi:10.1136/practneurol-2013-000790

Cited by 48 publications

(30 citation statements)

References 21 publications

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“…Delivering the news of a positive genetic test should be done face‐to‐face with the patient and his/her family. The option of referral to a specialist HD management clinic should also be available .…”

Section: Investigationsmentioning

confidence: 99%

Huntington's disease: a clinical review

McColgan

Tabrizi

2017

Euro J of Neurology

834

645

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Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6–13.7 individuals per 100 000. It is characterized by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments; therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently under way. This may bring us one step closer to treating and potentially preventing this devastating condition.

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Section: Investigationsmentioning

confidence: 99%

Huntington's disease: a clinical review

McColgan

Tabrizi

2017

Euro J of Neurology

834

645

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“…The patient requested genetic testing as a result of his sister's diagnosis. The patient and his wife were offered pre-test counseling for diagnostic testing, by the multidisciplinary team's who modelled the service after the example of Huntington's disease (Craufurd et al 2015). The patient decided to undergo genetic testing, and a formerly reported mutation (p.A382T) which is associated with an autosomal dominant form of ALS was found in exon 6 of TARDBP gene.…”

Section: Patientmentioning

confidence: 99%

Complexities of Genetic Counseling for ALS: A Case of Two Siblings with Discordant Genetic Test Results

Mandich

Mantero

Verdiani

et al. 2015

Journal of Genetic Counseling

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Rapid advances in the genetics of amyotrophic lateral sclerosis (ALS) have dramatically changed the approach of clinicians and researchers to the motor neuron diseases. We report two siblings in whom the genetic study provided conflicting results, hence raising a number of issues which deserve to be considered by clinicians involved in genetic testing for ALS. The first patient died within 2 years of ALS onset, while her brother still manages to walk unaided, 7 years into onset. Genetic analyses, performed on the first patient as part of a research protocol, and as clinical genetic testing on the brother, provided different results. Results for Patient 1 were negative for all investigated genes, thus suggesting that her disease may be a phenocopy, while her brother carried an autosomal dominant TARDBP mutation (p.A382T). A multidisciplinary approach may help patients and clinicians face the emerging dilemmas in such a complex field. Sharing and updating of advances, not to mention uncertainties inherent to current knowledge, with patients and families may prove to be an effective way to support them and to make them aware of the present limits of our knowledge and of the blurred border between research and clinical practice.

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“…Huntington’s disease (HD) is a rare progressive neurodegenerative disorder in which movement, behaviour and cognition are affected (Huntington 1872 ; Craufurd et al 2015 ). It affects approximately 3 individuals per 100,000 worldwide, with a higher prevalence of 10 per 100,000 in European populations (Harper 1992 ; Pringsheim et al 2012 ).…”

Section: Introductionmentioning

confidence: 99%

“…It affects approximately 3 individuals per 100,000 worldwide, with a higher prevalence of 10 per 100,000 in European populations (Harper 1992 ; Pringsheim et al 2012 ). It is a monogenic disorder that is autosomal dominantly inherited (Huntington 1872 ; Craufurd et al 2015 ) and is caused by an expansion of a CAG trinucleotide repeat in the gene huntingtin (HTT) (MacDonald et al 1993 ).…”

Section: Introductionmentioning

confidence: 99%

“It’s being part of the big picture, even though you’re a tiny jigsaw piece”—motivations and expectations of individuals participating in the Enroll-HD observational study

2020

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Predictive test guidelines for Huntington's disease (HD) recommend individuals are offered opportunities to participate in research regardless of test outcome. Consistent with most HD centres of excellence, the Manchester Centre for Genomic Medicine (MCGM) invites eligible individuals to participate in the observational study, Enroll-HD. Limited research has been conducted to date on the views of research participants and the possible impact of participation. The aim of this qualitative study was to explore the experiences of ten individuals taking part in the Enroll-HD study following pre-symptomatic testing for HD. Half of the individuals had tested positive for the HD mutation and the other half had tested negative. Participants were generally motivated to take part in the study by both personal and altruistic reasons. Overall, they were very positive about participation in Enroll-HD. Valuable aspects included good relationships with the research/clinical team, increased understanding of the condition, an enhanced self-image and a shared experience with affected parents. Issues for improvement to encourage participation included access to study site and more regular communication about study progress. Participants, while generally optimistic about research progress, were realistic about challenges.

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Diagnostic genetic testing for Huntington's disease

Cited by 48 publications

References 21 publications

Huntington's disease: a clinical review

Huntington's disease: a clinical review

Complexities of Genetic Counseling for ALS: A Case of Two Siblings with Discordant Genetic Test Results

“It’s being part of the big picture, even though you’re a tiny jigsaw piece”—motivations and expectations of individuals participating in the Enroll-HD observational study

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