Three novel FHL1 variants cause a mild phenotype of Emery‐Dreifuss muscular dystrophy

Abstract

Emery‐Dreifuss muscular dystrophy (EDMD) is a hereditary muscle disease, characterized by the clinical triade of early‐onset joint contractures, progressive muscle weakness, and cardiac involvement. Pathogenic variants in FHL1 can cause a rare X‐linked recessive form of EDMD, type 6. We report three men with novel variants in FHL1 leading to EDMD6. The onset of muscle symptoms was in late adulthood and muscle weakness was not prominent in either of the patients. All patients had hypertrophic cardiomyopathy and one of them also had cardiac arrhythmias. Western blot performed on muscle biopsies from two of the patients showed no FHL1 protein expression. We predict that the variant in the third patient also leads to the absence of FHL1 protein. Complete loss of all FHL1 isoforms combined with mild muscle involvement supports the hypothesis that loss of all FHL1 isoforms is more benign than the cytotoxic effects of expressed FHL1 protein with pathogenic missense variants.

Nova mutação no gene EMD em uma família brasileira com diagnóstico de distrofia muscular de Emery-Dreifuss: Dois relatos de caso e revisão da literatura

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