Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (441 page)

Other: Full-sequence analysis is required to detect rare loss-of-function mutations such as point mutations/small deletions. Methylation results from a chorionic villus sample may or may not reflect the accurate future status in the child.

HUNTINGTON DISEASE

MIM #143100

   Definition

Huntington disease (HD), autosomal dominant progressive neurodegenerative disorder, is caused by an expanded trinucleotide repeat (CAG)n, encoding glutamine, in the gene encoding huntingtin (HTT) on chromosome 4p16.3. HTT alleles are classified based on the size of the expansion:

   Normal alleles: 26 or fewer CAG repeats.

   Intermediate alleles: 27–35 CAG repeats. An individual with an allele in this range is not at risk of developing symptoms of HD, but because of instability in the CAG tract, may be at risk of having a child with an allele in the HD-causing range.

   HD-causing (full mutation) alleles: 36 or more CAG repeats. Individuals who have an allele with full mutation are considered at risk of developing HD in their lifetime.

   Relevant Tests and Diagnostic Value

   HTT (HD) is the only gene known to cause Huntington disease. A CAG repeat expansion is the only mutation observed.

   Clinical testing:

   PCR method to detect number of CAG trinucleotide repeats.

   Southern blot is used for confirmation of homozygous genotype and identification of large expansions.

   Predictive testing for at-risk asymptomatic adult family members requires prior confirmation of the diagnosis in the family using molecular genetic testing.

   Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior confirmation of the diagnosis in the family using molecular genetic testing.

Suggested Reading

Warby SC, Graham RK, Hayden MR. Huntington disease. In: Pagon RA, Adam MP, Bird TD, et al., eds.
GeneReviews
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[Internet]
. Seattle, WA: University of Washington, Seattle; 1998:1993– 2013 Oct 23 [Updated 2010 Apr 22]. Available from:
http://www.ncbi.nlm.nih.gov/books/ NBK1305/

LESCH-NYHAN SYNDROME

MIM #300322

   Definition