Three novel FHL1 variants cause a mild phenotype of Emery-Dreifuss muscular dystrophy.
EDMD6
Emery-Dreifuss muscular dystrophy
FHL1
cardiomyopathy
muscular dystrophy
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
14
04
2022
received:
26
11
2021
accepted:
22
05
2022
pubmed:
25
5
2022
medline:
5
8
2022
entrez:
24
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35607917
doi: 10.1002/humu.24415
pmc: PMC9545859
doi:
Substances chimiques
FHL1 protein, human
0
Intracellular Signaling Peptides and Proteins
0
LIM Domain Proteins
0
Muscle Proteins
0
Protein Isoforms
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1234-1238Informations de copyright
© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.
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