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Three novel FHL1 variants cause a mild phenotype of Emery‐Dreifuss muscular dystrophy
Author(s) -
Borch Josefine d. S.,
Krag Thomas,
HolmYildiz Sonja D.,
Cetin Hakan,
Solheim Tuva A.,
Fornander Freja,
Straub Volker,
Duno Morten,
Vissing John
Publication year - 2022
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24415
Subject(s) - muscular dystrophy , biology , missense mutation , muscle contracture , muscle weakness , gene isoform , phenotype , medicine , endocrinology , genetics , anatomy , gene
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.