Top

Published in:

Open Access 22-11-2023 | Duchenne Muscular Dystrophy | Review Article

Utility of exome sequencing for the diagnosis of pediatric-onset neuromuscular diseases beyond diagnostic yield: a narrative review

Authors: Martha Cecilia Piñeros-Fernández, Beatriz Morte, José Luis García-Giménez

Published in: Neurological Sciences | Issue 4/2024

Abstract

Diagnosis of neuromuscular diseases (NMD) can be challenging because of the heterogeneity of this group of diseases. This review aimed to describe the diagnostic yield of whole exome sequencing (WES) for pediatric-onset neuromuscular disease diagnosis, as well as other benefits of this approach in patient management since WES can contribute to appropriate treatment selection in NMD patients. WES increases the possibility of reaching a conclusive genetic diagnosis when other technologies have failed and even exploring new genes not previously associated with a specific NMD. Moreover, this strategy can be useful when a dual diagnosis is suspected in complex congenital anomalies and undiagnosed cases.

Benarroch L, Bonne G, Rivier F, Hamroun D (2023) The 2023 version of the gene table of neuromuscular disorders (nuclear genome). Neuromuscul Disord 33(1):76–117. https://doi.org/10.1016/j.nmd.2022.12.002

Deenen JCW, Horlings CGC, Verschuuren JJGM, Verbeek ALM, van Engelen BGM (2015) The epidemiology of neuromuscular disorders: a comprehensive overview of the literature. J Neuromuscul Dis 2:73–85CrossRefPubMed

Woodcock IR, Fraser L, Norman P, Pysden K, Manning S, Childs AM (2016) The prevalence of neuromuscular disease in the paediatric population in Yorkshire, UK; variation by ethnicity and deprivation status. Dev Med Child Neurol 58:877–883CrossRefPubMed

Kliest T, Van Eijk RPA, Al-Chalabi A et al (2022) Clinical trials in pediatric ALS: a TRICALS feasibility study. Amyotroph Lateral Scler Frontotemporal Degener. https://doi.org/10.1080/21678421.2021.2024856CrossRefPubMedPubMedCentral

Verhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC, Cook SF, Lochmüller H (2017) Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet J Rare Dis 12:1–15CrossRef

Huang K, Bi FF, Yang H (2021) A systematic review and meta-analysis of the prevalence of congenital myopathy. Front Neurol 12:1–10ADSCrossRef

Salari N, Fatahi B, Valipour E, Kazeminia M, Fatahian R, Kiaei A, Shohaimi S, Mohammadi M (2022) Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis. J Orthop Surg Res 17:1–12

Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Messina S, Trifirò G (2020) Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis. https://doi.org/10.1186/s13023-020-01430-8CrossRefPubMedPubMedCentral

Berg AO, Berg JS, Brown CW et al (2017) An evidence framework for genetic testing. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on the Health of Select Populations; Committee on the Evidence Base for Genetic Testing.Washington (DC): National Academies Press (US). https://doi.org/10.17226/24632

10.

Haskell GT, Adams MC, Fan Z et al (2018) Diagnostic utility of exome sequencing in the evaluation of neuromuscular disorders. Neurol Genet. https://doi.org/10.1212/NXG.0000000000000212CrossRefPubMedPubMedCentral

11.

Ghaoui R, Cooper ST, Lek M et al (2015) Use of whole-exome sequencing for diagnosis of limb-girdle muscular dystrophy: outcomes and lessons learned. JAMA Neurol 72:1424–1432CrossRefPubMed

12.

Chae JH, Vasta V, Cho A, Lim BC, Zhang Q, Eun SH, Hahn SH (2015) Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders. J Med Genet 52:208–216CrossRefPubMed

13.

Ankala A, Da Silva C, Gualandi F, Ferlini A, Bean LJH, Collins C, Tanner AK, Hegde MR (2015) A comprehensive genomic approach for neuromuscular diseases gives a high diagnostic yield. Ann Neurol 77:206–214CrossRefPubMed

14.

Beecroft SJ, Yau KS, Allcock RJN et al (2020) Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience. Ann Clin Transl Neurol 7:353–362CrossRefPubMedPubMedCentral

15.

Gonzalez-quereda L, Rodriguez MJ, Diaz-manera J, Alonso-perez J, Gallardo E, Nascimento A et al (2020) Targeted next-generation sequencing in a large cohort of genetically undiagnosed patients with neuromuscular disorders in Spain. Genes (Basel) 11(5):539. https://doi.org/10.3390/genes11050539

16.

Börklü-Yücel E, Demiriz Ç, Avcı Ş, Vanlı-Yavuz EN, Eraslan S, Oflazer P, Kayserili H (2020) Clinical exome sequencing in neuromuscular diseases: an experience from Turkey. Neurol Sci. https://doi.org/10.1007/s10072-020-04304-wCrossRefPubMed

17.

Lee H (2023) Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders. Dev Med Child Neurol. https://doi.org/10.1111/dmcn.15531CrossRefPubMed

18.

Shin JY, Chae JH, Choi M (2022) Transcriptome-based variant calling and aberrant mRNA discovery enhance diagnostic efficiency for neuromuscular diseases. J Med Genet 59(11):1075–1081. https://doi.org/10.1136/jmedgenet-2021-108307

19.

Wenger AM, Guturu H, Bernstein JA, Bejerano G (2017) Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers. Genet Med 19:209–214CrossRefPubMed

20.

Bullich G, Matalonga L, Pujadas M et al (2022) Systematic collaborative reanalysis of genomic data improves diagnostic yield in neurologic rare diseases. J Molec Diagn 24:529–542CrossRef

21.

Krenn M, Tomschik M, Rath J et al (2020) Genotype-guided diagnostic reassessment after exome sequencing in neuromuscular disorders: experiences with a two-step approach. Eur J Neurol 27:51–61CrossRefPubMed

22.

Tsang MHY, Chiu ATG, Kwong BMH et al (2020) Diagnostic value of whole-exome sequencing in Chinese pediatric-onset neuromuscular patients. Mol Genet Genomic Med 8(5):e1205. https://doi.org/10.1002/mgg3.1205

23.

Herman I, Lopez MA, Marafi D, Pehlivan D, Calame DG, Abid F, Lotze TE (2021) Clinical exome sequencing in the diagnosis of pediatric neuromuscular disease. Muscle Nerve 63:304–310CrossRefPubMed

24.

Waldrop MA, Pastore M, Schrader R, Sites E, Bartholomew D, Tsao CY, Flanigan KM (2019) Diagnostic utility of whole exome sequencing in the neuromuscular clinic. Neuropediatrics 50:96–102CrossRefPubMed

25.

Fattahi Z, Kalhor Z, Fadaee M, Vazehan R, Parsimehr E, Abolhassani A (2017) Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population. Clin Genet 91:386–402CrossRefPubMed

26.

Kuperberg M, Lev D, Blumkin L, Zerem A, Ginsberg M, Linder I, Carmi N, Kivity S, Lerman-Sagie T, Leshinsky-Silver E (2016) Utility of whole exome sequencing for genetic diagnosis of previously undiagnosed pediatric neurology patients. J Child Neurol 31:1534–1539CrossRefPubMed

27.

Masri AT, Oweis L, Qudah A, al, El-Shanti H, (2022) Congenital muscle dystrophies: role of singleton whole exome sequencing in countries with limited resources. Clin Neurol Neurosurg 217:107271CrossRefPubMed

28.

Schofield D, Alam K, Douglas L et al (2017) Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases. Genomic Med. https://doi.org/10.1038/s41525-017-0006-7CrossRef

29.

Vill K, Blaschek A, Gläser D et al (2017) Early-onset myopathies: clinical findings, prevalence of subgroups and diagnostic approach in a single neuromuscular referral center in Germany. J Neuromuscul Dis 4:315–325CrossRefPubMed

30.

O’Grady G, Monkol L, Lamande SR et al (2016) Diagnosis and aetiology of congenital muscular dystrophy – we are halfway there. Ann Neurol 80:101–11CrossRefPubMed

31.

Lee JM, Lim JG, Shin JH, Park YE, Kim DS (2017) Clinical and genetic diversity of nemaline myopathy from a single neuromuscular center in Korea. J Neurol Sci 383:61–68CrossRefPubMed

32.

Yiş U, Diniz G, Hazan F et al (2018) Childhood onset limb-girdle muscular dystrophies in the Aegean part of Turkey. Acta Myologica 37:210–220PubMedPubMedCentral

33.

Zamani GR, Mohammadi MF, Tavasoli AR et al (2022) Genetic analysis of forty MLPA-negative Duchenne muscular dystrophy patients by whole-exome sequencing. J Mol Neurosci 72:1098–1107CrossRefPubMed

34.

Luce LN, Carcione M, Mazzanti C, Ferrer M, Szijan I, Giliberto F (2018) Small mutation screening in the DMD gene by whole exome sequencing of an argentine Duchenne/Becker muscular dystrophies cohort. Neuromuscul Disord 28:986–995CrossRefPubMed

35.

Božović IB, Maver A, Leonardis L, Meznaric M, Osredkar D, Peterlin B (2021) Diagnostic yield of exome sequencing in myopathies: experience of a Slovenian tertiary centre. PLoS ONE 16:1–20

36.

Walsh M, Bell KM, Chong B et al (2017) Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy. Ann Clin Transl Neurol 4:318–325CrossRefPubMedPubMedCentral

37.

Todd EJ, Yau KS, Ong R et al (2015) Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth. Orphanet J Rare Dis 10:1–14CrossRef

38.

François-Heude MC, Walther-Louvier U, Espil-Taris C et al (2021) Evaluating next-generation sequencing in neuromuscular diseases with neonatal respiratory distress. Eur J Paediatr Neurol 31:78–87CrossRefPubMed

39.

Bittles AH, Black ML (2010) Consanguinity, human evolution, and complex diseases. Proc Natl Acad Sci U S A 107:1779–1786ADSCrossRefPubMedPubMedCentral

40.

Laitila J, Wallgren-Pettersson C (2021) Recent advances in nemaline myopathy. Neuromuscul Disord. https://doi.org/10.1016/j.nmd.2021.07.012CrossRefPubMed

41.

Birnkrant DJ, Bushby K, Bann CM et al (2018) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 17:251–267CrossRefPubMedPubMedCentral

42.

Kumar SH, Athimoolam K, Suraj M et al (2020) Comprehensive genetic analysis of 961 unrelated Duchenne Muscular Dystrophy patients: focus on diagnosis, prevention and therapeutic possibilities. PLoS ONE 15:1–22CrossRef

43.

Kramarz C, Rossor AM (2022) Neurological update: hereditary neuropathies. J Neurol. https://doi.org/10.1007/s00415-022-11164-1CrossRefPubMedPubMedCentral

44.

Sawyer SL, Hartley T, Dyment DA et al (2016) Utility of whole-exome sequencing for those near the end of the diagnostic odyssey : time to address gaps in care. Clin Genet 89:275–284CrossRefPubMed

45.

Niguidula N, Alamillo C, Shahmirzadi Mowlavi L, Powis Z, Cohen JS, Farwell Hagman KD (2018) Clinical whole-exome sequencing results impact medical management. Mol Genet Genomic Med 6:1068–1078CrossRefPubMedPubMedCentral

Title: Utility of exome sequencing for the diagnosis of pediatric-onset neuromuscular diseases beyond diagnostic yield: a narrative review
Authors: Martha Cecilia Piñeros-Fernández
Beatriz Morte
José Luis García-Giménez
Publication date: 22-11-2023
Publisher: Springer International Publishing
Keywords: Duchenne Muscular Dystrophy
Muscular Dystrophy
Muscular Dystrophy
Myopathy
Published in: Neurological Sciences / Issue 4/2024
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-023-07210-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Utility of exome sequencing for the diagnosis of pediatric-onset neuromuscular diseases beyond diagnostic yield: a narrative review

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2024

Malignant atrophic papulosis (Degos disease) with central nervous system involvement

A video-atlas of levodopa-induced dyskinesia in Parkinson’s disease: terminology matters

Use, experience and perspectives of high-density EEG among Italian epilepsy centers: a national survey

Transient side-changing hemispheric dysfunction: an unusual presentation of bilateral thalamic infarction mimicking large vessel occlusion

Blurred lines: bilateral optic perineuritis mimicking idiopathic intracranial hypertension

A seizure in the eye of the beholder: painting an absence-to-bilateral-tonic–clonic seizure