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Identification of novel FHL1 mutations associated with X-linked scapuloperoneal myopathy in unrelated Chinese patients

Journal of Human Genetics volume 68, pages 477–484 (2023)Cite this article

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Abstract

Mutations in the FHL1 gene can be associated with a variety of X-linked myopathies and cardiomyopathies, among which X-linked dominant scapuloperoneal myopathy is a rare phenotype. We collected the clinical data of two unrelated Chinese patients with X-linked scapuloperoneal myopathy and analyzed their clinical, pathological, muscle imaging, and genetic features. Both patients were characterized by scapular winging, bilateral Achilles tendon contractures, and weakness in shoulder-girdle and peroneal muscles. Muscle biopsy revealed myopathic changes, and no reducing bodies were found. Muscle magnetic resonance imaging was dominated by fatty infiltration, with minor edema-like findings. Genetic analysis revealed two novel mutations in the FHL1 gene: c.380T > C (p.F127S) and c.802C > T (p.Q268*), which were located in the LIM2 domain and the C-terminal sequence, respectively. To our knowledge, this is the first report of X-linked scapuloperoneal myopathy in the Chinese population. Our findings broadened the genetic and ethnic spectrum of FHL1-related disorders and proposed to look for variants in the FHL1 gene when scapuloperoneal myopathy is observed in the clinical work.

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References

  1. Cowling BS, Cottle DL, Wilding BR, D’Arcy CE, Mitchell CA, McGrath MJ. Four and a half LIM protein 1 gene mutations cause four distinct human myopathies: a comprehensive review of the clinical, histological and pathological features. Neuromuscul Disord. 2011;21:237–51.

    Article  PubMed  Google Scholar 

  2. Chen T, Lu X, Shi Q, Guo J, Wang H, Wang Q, et al. FHL1-related myopathy may not be classified by reducing bodies in muscle biopsy. Neuromuscul Disord. 2020;30:165–172.

    Article  PubMed  Google Scholar 

  3. Bertrand AT, Bönnemann CG, Bonne G, FHL1 Myopathy Consortium. 199th ENMC international workshop: FHL1 related myopathies, June 7-9, 2013, Naarden, the Netherlands. Neuromuscul Disord. 2014;24:453–62.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hu Z, Zhu Y, Liu X, Zhang W, Liu J, Wu S, et al. FHL1-related clinical, muscle MRI and genetic features in six Chinese patients with reducing body myopathy. J Hum Genet. 2019;64:919–26.

    Article  PubMed  Google Scholar 

  5. Mota IA, Correia CDC, Fontana PN, Carvalho AAS. Reducing body myopathy—a new pathogenic FHL1 variant and literature review. Neuromuscul Disord. 2021;31:847–53.

    Article  PubMed  Google Scholar 

  6. Malfatti E, Olivé M, Taratuto AL, Richard P, Brochier G, Bitoun M, et al. Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related disorders. J Neuropathol Exp Neurol. 2013;72:833–45.

    Article  CAS  PubMed  Google Scholar 

  7. Quinzii CM, Vu TH, Min KC, Tanji K, Barral S, Grewal RP, et al. X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1. Am J Hum Genet. 2008;82:208–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chen DH, Raskind WH, Parson WW, Sonnen JA, Vu T, Zheng Y, et al. A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations. J Neurol Sci. 2010;296:22–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Emmanuele V, Kubota A, Garcia-Diaz B, Garone C, Akman HO, Sánchez-Gutiérrez D, et al. Fhl1 W122S causes loss of protein function and late-onset mild myopathy. Hum Mol Genet. 2015;24:714–26.

    Article  CAS  PubMed  Google Scholar 

  10. Wilhelmsen KC, Blake DM, Lynch T, Mabutas J, De Vera M, Neystat M, et al. Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy. Ann Neurol. 1996;39:507–20.

    Article  CAS  PubMed  Google Scholar 

  11. Shalaby S, Hayashi YK, Goto K, Ogawa M, Nonaka I, Noguchi S, et al. Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1). Neuromuscul Disord. 2008;18:959–61.

    Article  PubMed  Google Scholar 

  12. Feldkirchner S, Walter MC, Müller S, Kubny C, Krause S, Kress W, et al. Proteomic characterization of aggregate components in an intrafamilial variable FHL1-associated myopathy. Neuromuscul Disord. 2013;23:418–26.

    Article  PubMed  Google Scholar 

  13. Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M, et al. Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet. 2009;85:338–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. D’Arcy C, Kanellakis V, Forbes R, Wilding B, McGrath M, Howell K, et al. X-linked recessive distal myopathy with hypertrophic cardiomyopathy caused by a novel mutation in the FHL1 gene. J Child Neurol. 2015;30:1211–7.

    Article  PubMed  Google Scholar 

  15. Wilding BR, McGrath MJ, Bonne G, Mitchell CA. FHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation. J Cell Sci. 2014;127:2269–81.

    CAS  PubMed  Google Scholar 

  16. Kadrmas JL, Beckerle MC. The LIM domain: from the cytoskeleton to the nucleus. Nat Rev Mol Cell Biol. 2004;5:920–31.

    Article  CAS  PubMed  Google Scholar 

  17. Pérez-Alvarado GC, Miles C, Michelsen JW, Louis HA, Winge DR, Beckerle MC, et al. Structure of the carboxy-terminal LIM domain from the cysteine rich protein CRP. Nat Struct Biol. 1994;1:388–98.

    Article  PubMed  Google Scholar 

  18. Cowling BS, McGrath MJ, Nguyen MA, Cottle DL, Kee AJ, Brown S, et al. Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy. J Cell Biol. 2008;183:1033–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mercuri E, Cini C, Counsell S, Allsop J, Zolkipli Z, Jungbluth H, et al. Muscle MRI findings in a three-generation family affected by Bethlem myopathy. Eur J Paediatr Neurol. 2002;6:309–14.

    Article  PubMed  Google Scholar 

  20. Schoser B, Goebel HH, Janisch I, Quasthoff S, Rother J, Bergmann M, et al. Consequences of mutations within the C terminus of the FHL1 gene. Neurology. 2009;73:543–51.

    Article  CAS  PubMed  Google Scholar 

  21. Morgan MJ, Madgwick AJ. The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle. Biochem Biophys Res Commun. 1999;255:245–50.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We sincere thank patients and their families for their participation.

Funding

This work was supported by the military training injury prevention research mission (21XLS28).

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Authors and Affiliations

  1. Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China

    Ying Lin, Juan Chen, Mengyang Liu, Jiaqi Liu & Qiang Shi

  2. Department of Neurology, First Hospital of Tsinghua University, Beijing, China

    Rui Ban

  3. Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China

    Lingya Qiao

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  1. Ying Lin
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  4. Juan Chen
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  6. Jiaqi Liu
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  7. Qiang Shi
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Contributions

Study conception and design: YL. Manuscript preparation: YL. Data acquisition: YL, RB, LQ, JC, ML, and JL. Critical review of the intellectual content: RB. Critical and important advice on the whole research conduction: QS.

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Correspondence to Qiang Shi.

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The authors declare no competing interests.

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The patient has provided consent for the use of the clinical information. This study has been approved by the Chinese PLA General Hospital Ethical Review Committee and has therefore been performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Lin, Y., Ban, R., Qiao, L. et al. Identification of novel FHL1 mutations associated with X-linked scapuloperoneal myopathy in unrelated Chinese patients. J Hum Genet 68, 477–484 (2023). https://doi.org/10.1038/s10038-023-01138-0

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