Clinical phenotype in carriers of intermediate alleles in the huntingtin gene.

Clinical phenotype in carriers of intermediate alleles in the huntingtin gene.

Publication date: Jul 15, 2019

To describe the phenotype of individuals with intermediate allele (IA) CAG repeat length in the huntingtin (HTT) gene evaluated at the Parkinson’s Disease Center and Movement Disorders Clinic (PDCMDC) at Baylor College of Medicine (BCM).

Huntington disease (HD) is caused by a mutation in the HTT gene of 36 or more CAG trinucleotide repeats. Since our original case report of pathologically proven HD with 29 CAG repeats, a growing body of evidence has accumulated supporting the observation that individuals with IA (27 to 35 CAG repeats) may exhibit clinical, imaging, and pathologic manifestations of HD. About 6% of the general population has CAG repeats in the IA range in at least one allele of the HTT gene. The presence of IA is a challenge for genetic counseling.

Medical records of patients with IAs seen at the PDCMDC at BCM from January 2008 to the present were reviewed to assess age at symptom onset, dominant clinical features and presence of psychiatric and cognitive symptoms.

Four men and five women were found to have IAs (range: 27-35) in the course of their evaluation at the PDCMDC. The age at onset of clinically evident symptoms ranged from 27 to 78 years. Six individuals had chorea, three had gait disturbance, two had stereotypies, and one patient had multiple motor tics. All nine had psychiatric symptoms, with depression being the most common.

Our series of 9 individuals with IA in the HTT gene exhibit a variety of motor and non-motor features that overlap with the HD phenotype. These individuals and their offspring should be considered at risk for development of progressive HD.

Savitt, D. and Jankovic, J. Clinical phenotype in carriers of intermediate alleles in the huntingtin gene. 06576. 2019 J Neurol Sci (402):

Concepts Keywords
Allele Clinical imaging
Alleles Counseling
Baylor Huntington’s disease
Chorea Branches of biology
Cognitive Genetic genealogy
Depression Medical genetics
Gait Disturbance Autosomal dominant disorders
Gene Huntingtin
Genetic Counseling Trinucleotide repeat disorders
Huntingtin Androgen receptor
Huntington
Movement Disorders
Mutation
Parkinson
Phenotype
Progressive
Sci
Stereotypies
Symptom
Trinucleotide Repeats

Semantics

Type Source Name
disease MESH development
disease MESH depression
disease MESH motor tics
disease MESH multiple
disease DOID chorea
disease MESH chorea
gene UNIPROT ELL
disease MESH men
disease DOID Huntington disease
disease MESH Huntington disease
gene UNIPROT TNFRSF17
disease MESH Movement Disorders
gene UNIPROT SLC6A4
gene UNIPROT HTT

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