Muscular Involvement and Tendon Contracture in Limb-girdle Muscular Dystrophy 2Y: a Mild Adult Phenotype and Literature Review

Overview

Journal BMC Musculoskelet Disord

Publisher Biomed Central

Specialties Orthopedics
Physiology

Date 2020 Sep 3

PMID 32873274

Citations 4

Authors

Xuelin Feng

Jinlang Wu

Wenbiao Xian

Bing Liao

Songjie Liao

Xiaoli Yao

Weixi Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Limb girdle muscular dystrophy type 2Y (LGMD2Y) is a rare subgroup of limb girdle muscular dystrophy featuring limb-girdle weakness, tendon contracture and cardiac involvement. It is caused by the mutation of TOR1AIP1, which encodes nuclear membrane protein LAP1 (lamina-associated polypeptide 1) and comprises heterogeneous phenotypes. The present study reported a patient with a novel homozygous TOR1AIP1 mutation that presented with selective muscle weakness, which further expanded the phenotype of LGMD2Y- and TOR1AIP1-associated nuclear envelopathies.

Case Presentation: A 40-year-old male presented with Achilles tendon contracture and muscle weakness that bothered him from 8 years old. While the strength of his distal and proximal upper limbs was severely impaired, the function of his lower limbs was relatively spared. Muscle pathology showed dystrophic features, and electron microscopy showed ultrastructural abnormalities of disrupted muscle nuclei envelopes. Whole-exome sequencing showed a frameshift mutation in TOR1AIP1 (c.98dupC).

Conclusion: We reported a novel mild phenotype of LGMD2Y with relatively selective distal upper limb weakness and joint contracture and revealed the heterogeneity of LGDM2Y and the role of the LAP1 isoform by literature review.

Citing Articles

LAP1 Interactome Profiling Provides New Insights into LAP1's Physiological Functions.

Pereira C, Espadas G, Martins F, Bertrand A, Servais L, Sabido E Int J Mol Sci. 2025; 25(24.

PMID: 39769001 PMC: 11678445. DOI: 10.3390/ijms252413235.

Quantitative proteome analysis of LAP1-deficient human fibroblasts: A pilot approach for predicting the signaling pathways deregulated in LAP1-associated diseases.

Pereira C, Espadas G, Martins F, Bertrand A, Servais L, Sabido E Biochem Biophys Rep. 2024; 39:101757.

PMID: 39035020 PMC: 11260385. DOI: 10.1016/j.bbrep.2024.101757.

-Associated Nuclear Envelopathies.

Mackels L, Liu X, Bonne G, Servais L Int J Mol Sci. 2023; 24(8).

PMID: 37108075 PMC: 10138496. DOI: 10.3390/ijms24086911.

Loss of the Nuclear Envelope Protein LAP1B Disrupts the Myogenic Differentiation of Patient-Derived Fibroblasts.

Kayman Kurekci G, Acar A, Dincer P Int J Mol Sci. 2022; 23(21).

PMID: 36362402 PMC: 9656778. DOI: 10.3390/ijms232113615.

Selective loss of a LAP1 isoform causes a muscle-specific nuclear envelopathy.

Lornage X, Mallaret M, Silva-Rojas R, Biancalana V, Giovannini D, Dieterich K Neurogenetics. 2021; 22(1):33-41.

PMID: 33405017 DOI: 10.1007/s10048-020-00632-3.

References

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

Kayman-Kurekci G, Talim B, Korkusuz P, Sayar N, Sarioglu T, Oncel I . Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: a novel gene related to nuclear envelopathies. Neuromuscul Disord. 2014; 24(7):624-33. DOI: 10.1016/j.nmd.2014.04.007. View

McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A . The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010; 20(9):1297-303. PMC: 2928508. DOI: 10.1101/gr.107524.110. View

. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002; 166(1):111-7. DOI: 10.1164/ajrccm.166.1.at1102. View

Worman H, Dauer W . The nuclear envelope: an intriguing focal point for neurogenetic disease. Neurotherapeutics. 2014; 11(4):764-72. PMC: 4391386. DOI: 10.1007/s13311-014-0296-8. View

Wang K, Li M, Hakonarson H . ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010; 38(16):e164. PMC: 2938201. DOI: 10.1093/nar/gkq603. View

Peng Y, Ye W, Chen Z, Peng H, Wang P, Hou X . Identifying Ataxia With Novel Mutations in a Chinese Population. Front Neurol. 2019; 9:1111. PMC: 6306413. DOI: 10.3389/fneur.2018.01111. View

Ghaoui R, Benavides T, Lek M, Waddell L, Kaur S, North K . TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle muscular dystrophy. Neuromuscul Disord. 2016; 26(8):500-3. DOI: 10.1016/j.nmd.2016.05.013. View

Brooke M, Griggs R, Mendell J, Fenichel G, Shumate J, Pellegrino R . Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981; 4(3):186-97. DOI: 10.1002/mus.880040304. View

10.

Kondo Y, Kondoh J, Hayashi D, Ban T, Takagi M, Kamei Y . Molecular cloning of one isotype of human lamina-associated polypeptide 1s and a topological analysis using its deletion mutants. Biochem Biophys Res Commun. 2002; 294(4):770-8. DOI: 10.1016/S0006-291X(02)00563-6. View

11.

Bhatia A, Mobley B, Cogan J, Koziura M, Brokamp E, Phillips J . Magnetic Resonance Imaging characteristics in case of TOR1AIP1 muscular dystrophy. Clin Imaging. 2019; 58:108-113. PMC: 6893088. DOI: 10.1016/j.clinimag.2019.06.010. View

12.

Zhang Q, Bethmann C, Worth N, Davies J, Wasner C, Feuer A . Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet. 2007; 16(23):2816-33. DOI: 10.1093/hmg/ddm238. View

13.

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S . The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016; 54:1.30.1-1.30.33. DOI: 10.1002/cpbi.5. View

14.

Lessel I, Chen M, Luttgen S, Arndt F, Fuchs S, Meien S . Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies. Hum Genet. 2020; 139(4):483-498. PMC: 7078146. DOI: 10.1007/s00439-019-02105-6. View

15.

Guglieri M, Straub V, Bushby K, Lochmuller H . Limb-girdle muscular dystrophies. Curr Opin Neurol. 2008; 21(5):576-84. DOI: 10.1097/WCO.0b013e32830efdc2. View

16.

Dorboz I, Coutelier M, Bertrand A, Caberg J, Elmaleh-Berges M, Laine J . Severe dystonia, cerebellar atrophy, and cardiomyopathy likely caused by a missense mutation in TOR1AIP1. Orphanet J Rare Dis. 2014; 9:174. PMC: 4302636. DOI: 10.1186/s13023-014-0174-9. View

17.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17(5):405-24. PMC: 4544753. DOI: 10.1038/gim.2015.30. View

18.

Santos M, Domingues S, Costa P, Muller T, Galozzi S, Marcus K . Identification of a novel human LAP1 isoform that is regulated by protein phosphorylation. PLoS One. 2014; 9(12):e113732. PMC: 4252041. DOI: 10.1371/journal.pone.0113732. View

19.

Nagano A, Koga R, Ogawa M, Kurano Y, Kawada J, Okada R . Emerin deficiency at the nuclear membrane in patients with Emery-Dreifuss muscular dystrophy. Nat Genet. 1996; 12(3):254-9. DOI: 10.1038/ng0396-254. View

20.

Mayhew A, Mazzone E, Eagle M, Duong T, Ash M, Decostre V . Development of the Performance of the Upper Limb module for Duchenne muscular dystrophy. Dev Med Child Neurol. 2013; 55(11):1038-45. DOI: 10.1111/dmcn.12213. View