The human skeletal muscle adenine nucleotide translocator gene maps to chromosome 4q35 in the region of the facioscapulohumeral muscular dystrophy locus

1993 ◽  
Vol 92 (2) ◽  
Author(s):  
Cisca Wijmenga ◽  
SaraT. Winokur ◽  
GeorgeW. Padberg ◽  
MetteI. Skraastad ◽  
MichaelR. Altherr ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Human Skeletal Muscle ◽  
Adenine Nucleotide ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Adenine Nucleotide Translocator ◽  
Gene Maps

The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle

Nature ◽  
1988 ◽  
Vol 333 (6172) ◽  
pp. 466-469 ◽  
Author(s):  
Elizabeth E. Zubrzycka-Gaarn ◽  
Dennis E. Bulman ◽  
George Karpati ◽  
Arthur H. M. Burghes ◽  
Bonnie Belfall ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gene Product ◽  
Human Skeletal Muscle ◽  
Duchenne Muscular Dystrophy Gene

scholarly journals Homozygous nonsense variant in LRIF1 associated with facioscapulohumeral muscular dystrophy

Neurology ◽  
2020 ◽  
Vol 94 (23) ◽  
pp. e2441-e2447 ◽  
Author(s):  
Kohei Hamanaka ◽  
Darina Šikrová ◽  
Satomi Mitsuhashi ◽  
Hiroki Masuda ◽  
Yukari Sekiguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Target Gene ◽  
Disease Gene ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Target Gene Expression ◽  
D4z4 Repeat ◽  
Biopsy Examination ◽  
Chromatin Relaxation

ObjectiveFacioscapulohumeral muscular dystrophy (FSHD) is a heterogenetic disorder predominantly characterized by progressive facial and scapular muscle weakness. Patients with FSHD either have a contraction of the D4Z4 repeat on chromosome 4q35 or mutations in D4Z4 chromatin modifiers SMCHD1 and DNMT3B, both causing D4Z4 chromatin relaxation and inappropriate expression of the D4Z4-encoded DUX4 gene in skeletal muscle. In this study, we tested the hypothesis whether LRIF1, a known SMCHD1 protein interactor, is a disease gene for idiopathic FSHD2.MethodsClinical examination of a patient with idiopathic FSHD2 was combined with pathologic muscle biopsy examination and with genetic, epigenetic, and molecular studies.ResultsA homozygous LRIF1 mutation was identified in a patient with a clinical phenotype consistent with FSHD. This mutation resulted in the absence of the long isoform of LRIF1 protein, D4Z4 chromatin relaxation, and DUX4 and DUX4 target gene expression in myonuclei, all molecular and epigenetic hallmarks of FSHD. In concordance, LRIF1 was shown to bind to the D4Z4 repeat, and knockdown of the LRIF1 long isoform in muscle cells results in DUX4 and DUX4 target gene expression.ConclusionLRIF1 is a bona fide disease gene for FSHD2. This study further reinforces the unifying genetic mechanism, which postulates that FSHD is caused by D4Z4 chromatin relaxation, resulting in inappropriate DUX4 expression in skeletal muscle.

scholarly journals DUX4 Signalling in the Pathogenesis of Facioscapulohumeral Muscular Dystrophy

2020 ◽  
Vol 21 (3) ◽  
pp. 729 ◽  
Author(s):  
Kenji Rowel Q. Lim ◽  
Quynh Nguyen ◽  
Toshifumi Yokota
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Transcription Factor ◽  
Muscular Dystrophy ◽  
Embryonic Development ◽  
Disease Onset ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Signalling Pathways ◽  
Progressive Muscle Weakness ◽  
Homeobox Protein

Facioscapulohumeral muscular dystrophy (FSHD) is a disabling inherited muscular disorder characterized by asymmetric, progressive muscle weakness and degeneration. Patients display widely variable disease onset and severity, and sometimes present with extra-muscular symptoms. There is a consensus that FSHD is caused by the aberrant production of the double homeobox protein 4 (DUX4) transcription factor in skeletal muscle. DUX4 is normally expressed during early embryonic development, and is then effectively silenced in all tissues except the testis and thymus. Its reactivation in skeletal muscle disrupts numerous signalling pathways that mostly converge on cell death. Here, we review studies on DUX4-affected pathways in skeletal muscle and provide insights into how understanding these could help explain the unique pathogenesis of FSHD.

scholarly journals Muscular dystrophy in a dish: engineered human skeletal muscle mimetics for disease modeling and drug discovery

2016 ◽  
Vol 21 (9) ◽  
pp. 1387-1398 ◽  
Author(s):  
Alec S.T. Smith ◽  
Jennifer Davis ◽  
Gabsang Lee ◽  
David L. Mack ◽  
Deok-Ho Kim
Keyword(s):  
Skeletal Muscle ◽  
Drug Discovery ◽  
Muscular Dystrophy ◽  
Human Skeletal Muscle ◽  
Disease Modeling

P.41Extra-skeletal muscle manifestations of facioscapulohumeral muscular dystrophy

2019 ◽  
Vol 29 ◽  
pp. S53
Author(s):  
C. Kelly ◽  
J. Saw ◽  
P. Thapa ◽  
J. Mandrekar ◽  
E. Naddaf
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Facioscapulohumeral Muscular Dystrophy

Characterisation of dystrophin during development of human skeletal muscle

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 395-402 ◽  
Author(s):  
A. Clerk ◽  
P.N. Strong ◽  
C.A. Sewry
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Human Skeletal Muscle ◽  
Gradual Increase ◽  
Differential Staining ◽  
Relative Molecular Mass ◽  
Adult Tissue ◽  
Dmd Gene

Dystrophin, the 427 × 10(3) Mr product of the Duchenne muscular dystrophy (DMD) gene, was studied in human foetal skeletal muscle from 9 to 26 weeks of gestation. Dystrophin could be detected from at least 9 weeks of gestation at the sarcolemmal membrane of most myotubes, though there was differential staining with antibodies raised to various regions of the protein. Dystrophin immunostaining increased and became more uniform with age and by 26 weeks of gestation there was intense sarcolemmal staining of all myotubes. On a Western blot, a doublet of smaller relative molecular mass than that seen in adult tissue was detected in all foetuses studied. There was a gradual increase in abundance of the upper band from 9 to 26 weeks, and the lower band, although present in low amounts in young foetuses, increased significantly between 20 and 26 weeks of gestation. These data indicate that there are several specific isoforms of dystrophin present in developing skeletal muscle, though the role of these is unknown.

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