Adellgene® Huntington Disease

Huntington Disease (HD) is a progressive disorder of motor, cognitive, and psychiatric disturbances. The disease is inherited in an autosomal dominant fashion and is caused by the expansion of CAG trinucleotide repeats located in a gene termed Huntingtin (HTT, originally known as IT-15). This trinucleotide codes for the aminoacid glutamine.

A normal allele for gene HTT contains 6-26 CAG repeats. Individuals with 27-35 repeats fall into the intermediate range, and their children are at risk of HD. From 36 to 39 repeats are considered alleles with reduced (or incomplete) penetrance, and individuals may or may not develop HD. Alleles with more than 40 repeats will lead to the development of the disease and are considered fully penetrant alleles.

INTENDED USE

Adellgene® Huntington Disease is a semi-automated in vitro diagnostic kit designed for use in clinical laboratories, for the quantitative determination of the number of repetitions of the CAG (cytosine-adenine-guanine) triplet, located on exon 1 of the IT15 gene (HTT), which can result in the formation of Huntington’s disease (HD), also called Huntington’s Chorea.

It aims to aid the clinical diagnosis of Huntington’s chorea. The kit allows the quantification of the size of normal, intermediate and pathogenic alleles with a size equal to or less than 200 repeats. The expansions of more than 200 repeats can be detected, but not quantified.

The procedure is based on the amplification by Triplet repeat Primed Polymerase Chain Reaction (TP-PCR) with fluorescent primers of genomic DNA extracted from whole blood and/or buccal swab, subsequent analysis of the amplified products in a capillary sequencer and number of repeats calculation from the corresponding amplified product size.

The patient referred by the corresponding health specialist (for example, neurologist), may be subjected to the determination of the number of CAG triplets in exon 1 of the HTT gene taking into account the compatibility of the symptoms presented (progressive motor disability featuring chorea, mental disturbances including cognitive decline, changes in personality, and/or depression), and/or family history.

The intended user of the kit is technical personnel trained to carry out the protocol and the interpretation of results described in the instructions for use.

WORKFLOW:

RESULTS:

Sample with one normal allele and one intermediate allele.

Sample with one normal allele and one fully penetrant allele (<200 repeats).

Sample with one normal allele and one fully penetrant allele (>200 repeats).

Limitations

–  Mutations (point mutations, insertions, deletions) at amplification primer sites are possible and may result in the lack of allele definition. Other technologies could be necessary to resolve the genotyping.

–  Data and result interpretation should be revised by qualified personnel.