Huntington disease and the mechanisms of neuronal death

Abstract

Huntington disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansions in the Huntington HTT gene inherited in an autosomal dominant manner. It is characterized by a motor, cognitive and psychiatric symptoms that progress to death within 10-20 years. Herein we report two families with a dysfunction in the HTT gene causing a motor progression and cognitive deterioration. Indeed, both affected patients reported similar symptomatology characterized by involuntary movements (chorea), general motor impairment, depression and cognitive disorder. In order to detect the CAG-repeat in the HTT gene, a real time PCR analysis was performed. The diagnosis was confirmed because of the presence of a CAG trinucleotide repeat expansions in the HTT gene exceeding 35 repetitions. Thereby, the genetic counselling has been established and recommended for the other family members.
 The HTT gene localized on 4p16.3 encodes for Huntington protein. CAG trinucleotide expansion in the HTT gene encodes for an abnormal polyglutamine tract in the huntingtin protein. The Huntington disease manifests when the number of the triplet is more than 35 repetitions causing an apoptosis in striatal neurons with a dysfunction in cytoplasm functions. The exact molecular mechanism by which the mutant huntingtin protein induces cell death as well as its function are not totally understood. Genetic confirmation of the diagnosis is important for patient’s management and genetic counselling. Many therapeutic options are available for treating symptoms with a focus on life quality improve. 
 Keywords: Huntington disease, Triplet expansion, Neuronal apoptosis.