To read the full article by Elisa Di Giorgio*,Silvia Benavides-Varela, Annamaria Porru,Sara Caviola,Marco Lunghi,Paola Rigo,Giovanna Mioni, Giulia Calignano, Martina Annunziata, Eloisa Valenza,Valentina Liani,Federica Beghetti, Fabiola Spolaor, Elisa Bettella, Roberta Polli, Zimi Sawacha, and Alessandra Murgia, please click here. 

*Professor Di Giorgio currently serves on FraXI’s board of advisors. You can explore more of the Padua Fragile X Centre’s transnational research here. 

What is Activation Ratio (AR)? 

Variation of phenotypes among females with full mutation FXS may be attributed to a phenomenon known as ‘X inactivation’. Studying the activation ratio (AR), which represents the fraction of the normal allele or alternative forms or variations of the gene carried on the active X chromosome, has been shown to be helpful in attempting to understand the nature of many X-linked conditions. However, the relationship between AR and female carriers of the FXS full mutation has so far been neglected by researchers. 

Studien 

The authors of this new study were able to compare the cognitive, neuropsychological, adaptive, and behavioral profile of two girls diagnosed as FXS full mutation carriers, aged 10 and 11 who had identical FMR1 genotypic profile of full mutation but different AR levels (70% and 30% respectively). The study aimed to investigate the impact of AR on phenotypical functioning of the girls by following an innovative multi-method protocol that combined molecular investigation, gait analysis, lab-based experimental tasks, neuropsychological testing, and parent-reports questionnaire.

The Findings 

Lower AR was found to correspond to worse performances in many areas considered, but not all of them. From a cognitive and adaptive level, for example, the two girls differed in terms of IQ. There were no differences observed between the two at the behavioural level except for borderline scores for social withdrawal problems and depression in one of the girls.

Implicit and explicit time processing could be preserved even with lower AR. The authors found that in terms of performance in a visual rhythmic task, the younger girl fared better than the older. They call for more research on why this may be the case as this result suggests that some basic skills can be preserved even with a lower AR.

The girls’ maths skills appeared to be better preserved with higher AR. As mathematical skills are widely believed to be an area that needs improvement in premutation females as well as girls living with FXS, this finding is important because it suggests that mathematical abilities may be preserved in females with full mutation but high AR. More research focusing on this particular finding is needed. 

In the Responding Joint Attention (RJA) task, both girls responded similarly but the descriptive visualisations showed distinctions in their attention strategies. The authors call for future research to investigate whether data distribution analysis reveals individual differences, particularly in more complex abilities like initiating joint attention.

Overall, the study highlights that intensive study of the relationship between AR and neurobehavioural outcomes in female carriers of the full mutation is worth supporting.