The gender effect in juvenile Huntington disease patients of Italian origin

We analyzed a population of juvenile Huntington disease (HD) subjects of Italian origin (n = 57). The main aim of this study was to analyze the gender effect of the affected parent on age at onset and clinical presentation of offspring with juvenile HD. We also analyzed molecular features of the disease, including CAG mutation length and GluR6 gene polymorphism, according to the affected parent's gender. The mutation length was longer in paternally than in maternally transmitted HD juvenile patients (P = 0.025), nevertheless a similar mean early onset in the two groups (P > 0.05). This data was even enforced by that obtained from the whole cohort of patients included in the databank (n = 600) where, in the presence of increased mean parent-child CAG repeat change in paternal vs. maternal meiotic transmissions (+7.3 vs. +0.7 CAG, P = 0.0002), the mean parent-child year-of-onset change was similar in the two groups (-10.4 and -7.0 years, P > 0.05). A lower TAA-triplet in GluR6 was associated with an earlier age at onset in juvenile patients (P = 0.031, R2 = 0.10). When we added the GluR6 effect on age at onset to the CAG expanded number effect (P = 0.0001, R2 = 0.68) by multiple regression approach, the coefficient of determination R2 increased to 0.81. This effect in addition to the expanded CAG repeat number, found in juvenile and not in adult patients, was slightly enforced by paternal compared to maternal transmissions (R2=0.82). Our findings suggest the occurrence of a weaker effect of the paternal mutation on juvenile age at onset in our population, possibly amplified by other genetic factors, such as the TAA-triplet length in the GluR6 gene.