Involvement of the brain orexin system in a familial form of anorexia nervosa.

BACKGROUND

Anorexia nervosa (AN) is a debilitating eating disorder. To date, very few genes have been identified that predispose to AN.

AIM: An alternative to association studies is the characterisation of ultra-rare variants in familial forms of AN.

METHODS

Here, we use this approach to identify molecular pathways that contribute to the development of AN by analysing one family with two members suffering from AN by trio whole-exome analysis.

RESULTS

We identified an ultra-rare deleterious variant c.199 + 2T > G in the HCRTR1 gene in the two affected females in the family. The in vitro minigene assay confirmed that c.199 + 2T > C resulted in exon 3 skipping, leading to the loss of the start initiation codon.

CONCLUSION

This HCRTR1 gene, known to be involved in the regulation of feeding and physical activity, and already implicated in the reward pathway, may play a predisposing role in AN, at least in familial forms.

CORE TIP: Anorexia nervosa (AN) is a debilitating eating disorder. To date, only a few genes have been identified as predisposing to AN. The HCRTR1 gene is known to be involved in the regulation of feeding and physical activity. The identification of a rare loss-of-function variant in HCRTR1 strongly suggests that the orexin pathway may be involved in the predisposition to anorexia nervosa.