Technical Standards and Guidelines for Huntington Disease Testing

Potter, Nicholas; Spector, Elaine; Prior, Thomas W.

doi:10.1097/01.gim.0000106165.74751.15

Cited by 85 publications

(74 citation statements)

References 31 publications

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“…Juvenile-onset HD occurs in 5% of HD patients and is genetically characterized by very large CAG repeats and a predominance of paternal inheritance [Potter et al, 2004]. Our case is unique because the approximately þ60 CAG repeat expansion observed in our patient constitutes the largest molecularly confirmed intergenerational expansion that occurred through maternal transmission.…”

Section: Discussionmentioning

confidence: 65%

“…The neurological decline is progressive and leads to death approximately 20 years after onset of symptoms. It is inherited in an autosomal dominant pattern with a prevalence of approximately 1 per 10,000 individuals [Potter et al, 2004;Wexler et al, 2004]. In 1993, the HD gene was cloned and the causal mutation was discovered.…”

Section: Introductionmentioning

confidence: 99%

“…The expanded CAG repeat encoding polyglutamine results in a toxic huntingtin protein leading to cell death of neuronal tissue particularly within the putamen and caudate nuclei [Young, 2003]. The number of CAG repeats is usually inversely proportional to the age of onset of the first symptoms of HD [Potter et al, 2004;Wexler et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

“…Juvenileonset HD before the age of 20 years occurs in about 5% of HD cases [Potter et al, 2004], and is associated with very large ( 60) CAG repeat expansions [Nance and Myers, 2001]. Maternal expansion of the CAG repeats is reported in only 20% of juvenile cases of HD [Hayden et al, 1981] and rarely expands beyond þ20 repeats [Sanchez et al, 1997].…”

Section: Introductionmentioning

confidence: 99%

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Juvenile onset Huntington disease resulting from a very large maternal expansion

Nahhas

Garbern

Krajewski

et al. 2005

American J of Med Genetics Pt A

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We report a 5½‐year‐old girl with a maternal family history of Huntington disease (HD), who presented clinically with unbalanced gait, impaired speech, and increasing difficulty with fine motor control. Onset of symptoms began at the age of 3½ years. The suspected diagnosis of juvenile HD, based upon her family history, was confirmed by DNA analysis. At age 7, the patient died secondary to complications of her underlying disorder. Juvenile‐onset Huntington disease is uncommon, predominantly transmitted by fathers and is always associated with very large expansions of the CAG repeat. Interestingly, this patient inherited a large CAG size expansion from her mother, who herself had symptoms of HD at the age of 18. Molecular analysis revealed that the mother had 70 CAG repeats whereas our patient had ∼130 CAG repeats. This is the largest reported CAG expansion from a maternal transmission that has been confirmed molecularly and it demonstrates that very large expansions can also occur through the maternal lineage. © 2005 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Juvenile onset Huntington disease resulting from a very large maternal expansion

Nahhas

Garbern

Krajewski

et al. 2005

American J of Med Genetics Pt A

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“…In the current analysis, we also include simulated grading based on allele sizing, using criteria from the ACMG Huntington Disease Standards and Guidelines, 3 which is an update to an earlier document on the same topic. 7 Grading of the allele size began in 2011 and requires that laboratories both accurately size and interpret these alleles. Herein, we analyze CAP/ACMG HD survey challenges from 2003 to 2010 to answer four main questions: (1) among current participants in the Survey, how many clinical tests are performed and what is the turn-around time?…”

Section: Introductionmentioning

confidence: 99%

Assessing the analytic validity of molecular testing for Huntington disease using data from an external proficiency testing survey

Palomaki

Richards

2012

Genetics in Medicine

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original research article Purpose: Documenting high analytic validity of the molecular diagnostic test for Huntington disease is important because of counseling implications. This dominantly inherited adult onset disorder (prevalence of three or more per 100,000) is characterized by chorea, ataxia, and personality changes. The molecular basis is excessive CAG repeats in the HTT gene. methods:External proficiency testing survey results for Huntington disease were extracted (2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010). Analytic interpretations and CAG repeat lengths were compared with published performance criteria.Results: Between 2008 and 2010, 33 US participating laboratories reported clinical test interpretations. Analytic validity was high (sensitivity: 99.5%, 95% confidence interval: 97.1-99.9%; specificity: 99.2%, 95% confidence interval: 97.1-99.9%). Repeat length errors occurred in 2.6% (95% confidence interval: 1.8-3.8%) of 1,060 allelic challenges, with most being minor or from a single participant. Past performance (2003)(2004)(2005)(2006)(2007) was similar. The 23 international participants had more total repeat length errors (17.5%, 95% confidence interval: 14.6-20.7%). Further analyses indicated that assessment criteria can be relaxed without jeopardizing analytic validity.conclusion: Analytic validity is high for Huntington disease testing among US laboratories. International survey participants had lower analytic validity and a higher proportion of poorly performing laboratories. The reasons for this are unclear.Genet Med 2012:14(1):69-75

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Huntington Disease: Molecular Diagnostics Approach

Baştepe

Xin

2015

CP Human Genetics

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Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at-risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed.

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Technical Standards and Guidelines for Huntington Disease Testing

Cited by 85 publications

References 31 publications

Juvenile onset Huntington disease resulting from a very large maternal expansion

Juvenile onset Huntington disease resulting from a very large maternal expansion

Assessing the analytic validity of molecular testing for Huntington disease using data from an external proficiency testing survey

Huntington Disease: Molecular Diagnostics Approach

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