DMD Mutations in Pediatric Patients with Phenotypes of Duchenne/Becker Muscular Dystrophy

Overview

Journal Open Med (Wars)

Specialty General Medicine

Date 2024 Nov 26

PMID 39588385

Authors

Liping Ge

Yang Yang

Yanfei Yang

Yanfei Chen

Na Tao

Liping Zhang

Canmiao Zhao

Xing Zhang

Affiliations

Soon will be listed here.

Abstract

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-inherited neuromuscular diseases. The genetic diagnosis has been used as the diagnostic choice for DMD/BMD. The study subjects consisted of 37 patients from Southwest China. Peripheral blood was collected for the extraction of genomic DNA. DMD mutation was sequenced using the next-generation sequencing approach. The detected mutation was validated using the multiplex ligation-dependent probe amplification or Sanger sequencing methods. Variation annotation and pathogenicity prediction were performed using the online databases. Pathogenic mutations were identified 3 splicing site, 7 single nucleotide, 1 indel, 23 deletion, and 3 duplication mutations. Novel DMD variants were discovered, including two novel splicing variations (c.1890 + 1G>T; c.1923 + 1G>A), one missense mutation (c.1946G>T), one nonsense mutation (c.7441G>T), one indel mutation (INDEL EX20), and one duplication mutation (DUP EX75-78). The current study provides mutation information of DMD for the genetic diagnosis of DMD/BMD.

References

Chen H, Chin Y, Lundy D, Liang C, Chi Y, Kuo P . Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis. Sci Rep. 2017; 7(1):7372. PMC: 5547154. DOI: 10.1038/s41598-017-05993-8. View

Khelifi M, Ishmukhametova A, Khau Van Kien P, Thorel D, Mechin D, Perelman S . Pure intronic rearrangements leading to aberrant pseudoexon inclusion in dystrophinopathy: a new class of mutations?. Hum Mutat. 2011; 32(4):467-75. DOI: 10.1002/humu.21471. View

. Database Resources of the National Genomics Data Center, China National Center for Bioinformation in 2022. Nucleic Acids Res. 2021; 50(D1):D27-D38. PMC: 8728233. DOI: 10.1093/nar/gkab951. View

Garcia-Rodriguez R, Hiller M, Jimenez-Gracia L, van der Pal Z, Balog J, Adamzek K . Premature termination codons in the gene cause reduced local mRNA synthesis. Proc Natl Acad Sci U S A. 2020; 117(28):16456-16464. PMC: 7368324. DOI: 10.1073/pnas.1910456117. View

Torella A, Zanobio M, Zeuli R, Del Vecchio Blanco F, Savarese M, Giugliano T . The position of nonsense mutations can predict the phenotype severity: A survey on the DMD gene. PLoS One. 2020; 15(8):e0237803. PMC: 7437896. DOI: 10.1371/journal.pone.0237803. View

Djinovic-Carugo K, Young P, Gautel M, Saraste M . Structure of the alpha-actinin rod: molecular basis for cross-linking of actin filaments. Cell. 1999; 98(4):537-46. DOI: 10.1016/s0092-8674(00)81981-9. View

Verhaart I, Aartsma-Rus A . Therapeutic developments for Duchenne muscular dystrophy. Nat Rev Neurol. 2019; 15(7):373-386. DOI: 10.1038/s41582-019-0203-3. View

Koczok K, Mero G, Szabo G, Madar L, Gombos E, Ajzner E . A novel point mutation affecting Asn76 of dystrophin protein leads to dystrophinopathy. Neuromuscul Disord. 2018; 28(2):129-136. DOI: 10.1016/j.nmd.2017.12.003. View

Adzhubei I, Schmidt S, Peshkin L, Ramensky V, Gerasimova A, Bork P . A method and server for predicting damaging missense mutations. Nat Methods. 2010; 7(4):248-9. PMC: 2855889. DOI: 10.1038/nmeth0410-248. View

10.

Guevara-Fujita M, Huaman-Dianderas F, Obispo D, Sanchez R, Barrenechea V, Rojas-Malaga D . MLPA followed by target-NGS to detect mutations in the dystrophin gene of Peruvian patients suspected of DMD/DMB. Mol Genet Genomic Med. 2021; 9(9):e1759. PMC: 8457708. DOI: 10.1002/mgg3.1759. View

11.

Fagerberg L, Hallstrom B, Oksvold P, Kampf C, Djureinovic D, Odeberg J . Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2013; 13(2):397-406. PMC: 3916642. DOI: 10.1074/mcp.M113.035600. View

12.

Legardinier S, Raguenes-Nicol C, Tascon C, Rocher C, Hardy S, Hubert J . Mapping of the lipid-binding and stability properties of the central rod domain of human dystrophin. J Mol Biol. 2009; 389(3):546-58. DOI: 10.1016/j.jmb.2009.04.025. View

13.

Bucher F, Friedlander M, Aguilar E, Kurihara T, Krohne T, Usui Y . The long dystrophin gene product Dp427 modulates retinal function and vascular morphology in response to age and retinal ischemia. Neurochem Int. 2019; 129:104489. DOI: 10.1016/j.neuint.2019.104489. View

14.

Zhao J, Kodippili K, Yue Y, Hakim C, Wasala L, Pan X . Dystrophin contains multiple independent membrane-binding domains. Hum Mol Genet. 2016; 25(17):3647-3653. PMC: 5216612. DOI: 10.1093/hmg/ddw210. View

15.

Wagner K, Kuntz N, Koenig E, East L, Upadhyay S, Han B . Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve. 2021; 64(3):285-292. PMC: 9290993. DOI: 10.1002/mus.27347. View

16.

Corvelo A, Hallegger M, Smith C, Eyras E . Genome-wide association between branch point properties and alternative splicing. PLoS Comput Biol. 2010; 6(11):e1001016. PMC: 2991248. DOI: 10.1371/journal.pcbi.1001016. View

17.

Chang W, Iannaccone S, Lau K, Masters B, McCabe T, McMillan K . Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proc Natl Acad Sci U S A. 1996; 93(17):9142-7. PMC: 38609. DOI: 10.1073/pnas.93.17.9142. View

18.

Gao Q, McNally E . The Dystrophin Complex: Structure, Function, and Implications for Therapy. Compr Physiol. 2015; 5(3):1223-39. PMC: 4767260. DOI: 10.1002/cphy.c140048. View

19.

Duan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A . Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021; 7(1):13. PMC: 10557455. DOI: 10.1038/s41572-021-00248-3. View

20.

Okubo M, Minami N, Goto K, Goto Y, Noguchi S, Mitsuhashi S . Corrigendum: Genetic diagnosis of Duchenne/Becker muscular dystrophy using next-generation sequencing: validation analysis of DMD mutations. J Hum Genet. 2017; 62(10):931-933. PMC: 7609325. DOI: 10.1038/jhg.2017.54. View