Phenotypic spectrum and sex effects in eleven myoclonus‐dystonia families with ε‐sarcoglycan mutations

Abstract

Myoclonus-dystonia (M-D) due to SGCE mutations is characterized by early onset myoclonic jerks, often associated with dystonia. Penetrance is influenced by parental sex, but other sex effects have not been established. In 42 affected individuals from 11 families with identified mutations, we found that sex was highly associated with age at onset regardless of mutation type; the median age onset for girls was 5 years versus 8 years for boys (P < 0.0097). We found no association between mutation type and phenotype.

Myoclonus-dystonia: clinical and genetic evaluation of a large cohort

“…There is evidence that missense mutations in the SGCE gene lead to protein degradation and thus also to loss of function 11. Recently, an association between gender and age at onset has been reported in mutation carriers with girls having an earlier age of onset 20. We could not confirm these findings in our small number of gene positive cases.…”

Cœur et sarcoglycanopathies

“…Le complexe sarcoglycane est composé de quatre glycoproté ines transmembranaires (a, b, g, d) qui font partie de la famille des sarcospanes (Hoshio et al, 1987). Ré cemment, une autre glycoproté ine a é té identifié e ; il s'agit de l'e-sarcoglycane (Raymond et al, 2008) ; cette derniè re pré sente une grande homologie avec l'a-sarcoglycane. La dystrophine interagit avec la g-sarcoglycane, alors que la d-sarcoglycane est relié e avec le complexe dystroglycane.…”

A gain-of-glycosylation mutation associated with myoclonus-dystonia syndrome affects trafficking and processing of mouse ε-sarcoglycan in the late secretory pathway

“…Missense mutations are associated with approximately 15% of MDS cases [Grunewald et al, 2008;Tezenas du Montcel et al, 2006]. Our recent literature survey of published MDS cases identified 13 novel missense mutations [Gerrits, 2006;Hedrich et al, 2004;Hjermind et al, 2003;Klein et al, 2002;Leung et al, 2001;Nardocci et al, 2008;Raymond et al, 2008;Ritz et al, 2009;Roze et al, 2008;Schule et al, 2004;Tezenas du Montcel et al, 2006] (Supp . Table S1).…”

“…Most of these mutations conform to a loss-of-function model for the disease with no apparent mutation-dependent phenotype associations [Grunewald et al, 2008;Raymond et al, 2008]. Rare heterozygous genomic deletions have also been identified as a cause of MDS.…”