Disease-modifying factors in inherited muscle diseases, a twin study
Phenotypic variation has been reported in patients with the same inherited muscle disease, even with identical gene mutations, inter- and intrafamilially.
The goal of this project is
(i) to investigate if there is a variability in onset, progression and symptoms in monozygotic and dizygotic twins with inherited muscle diseases, with primary focus on muscular dystrophies like dysferlinopathies.
(ii) to identify disease-modifying factors (epigenetic or environmental) in twins with inherited muscle disorders, which is important for development of new therapeutic strategies.
First, we will identify twins with inherited muscle diseases, selected after crosslinked data from the globally biggest known Twin Registry at Karolinska Institutet and the national patient registry in Sweden, followed by validation of diagnosis reviewing medical records. Twin pairs with a genetically verified muscle disease will be eligible for further investigations (clinical examination, surveys and current functional status). Individuals with suspected inherited muscle disease but without specified diagnosis will be after informed consent screened for a numerous amount of known mutations leading to inherited muscle diseases using a targeted gene panel (>236 exons). Comparing both members within a twinpair in regard to disease onset, progression may show variations /differences, suggesting presence of disease-modifying factors, that further needs to be identified retrospectively.