Congenital Mirror Movements (CMM) is a rare neurodevelopmental disorder, characterized by voluntary movements from one side of the body that are mirrored by involuntary movements on the opposite side. It is considered a disorder of axonal guidance, and affected individuals have abnormalities in the corticospinal tract. We have performed whole exome sequencing in a large autosomal dominant family with CMM and identified a frameshift variant in ARHGEF7 segregating with the CMM phenotype, c.1751_1752del that leads to p.Asn584Thrfs*90. The purpose of this study is to validate the role of ARHGEF7 in the pathogenesis of CMM. We are using the zebrafish model to investigate whether this variant is pathogenic and to further understand its mode of action. We have created a CRISPR-induced knockout mutant at Arhgef7, and we will conduct overexpression assays in zebrafish. We will perform behavioral analyses and examine axonal defects using immunostaining. This project aligns with the missions of CERMO-FC because CMM is considered an orphan disease, with no known effective treatments. With over 35 individuals diagnosed with CMM in Quebec alone, our research findings will be presented at scientific conferences to further the public’s knowledge of this disease and will directly impact the community.

Name: Meagan Collins, B.Sc
Supervisor: Zoha Kibar (McGill)
Laureate: Master’s scholarship 2018