A new gene for autosomal dominant facial palsy/migraine identified in a family by whole exome sequencing

Abstract

AbstractBackgroundFacial palsy manifests as unilateral or bilateral weakness and inability to move some of the facial muscles. The aetiology may be different including idiopathic, trauma, infections or brain tumours or it can be associated with chronic neurological diseases. For instance, in recurrent migraine, an increased risk of idiopathic facial palsy (often unilateral) has been observed. Migraine is a neurovascular disorder characterized by mild to severe intensity of headaches, often associated with neuro‐ophthalmological symptoms.MethodsA family is reported where five members were affected by facial palsy associated with other clinical features including migraine, diplopia, facial swelling, eye conjunctivitis following a vertical transmission. Whole exome sequencing was performed in three members (two affected and one healthy) in order to identify potential variants causative of their phenotype.ResultsA missense variant c.304G>A was found leading to the p.(Ala102Thr) substitution in the TRPM8 gene, previously related to migraine by genome wide association studies. This variant was classified as deleterious by several predictor tools, and the mutant residue was predicted to alter the protein structure in terms of flexibility and interactions with the surrounding residues.ConclusionThese findings suggest that TRPM8 could be a new causative gene further linking migraine and recurrent facial palsy.