Neonatal Medicine

The Korean Society of Neonatology (대한신생아학회)
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A Korean Case of Neonatal Nemaline Myopathy Carrying KLHL40 Mutations Diagnosed Using Next Generation Sequencing

  • Suh, Yoong-a (Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine) ;
  • Sohn, Young Bae (Department of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine) ;
  • Park, Moon Sung (Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine) ;
  • Lee, Jang Hoon (Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine)
  • Received : 2021.02.02
  • Accepted : 2021.05.10
  • Published : 2021.05.31
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Abstract

Nemaline myopathy is a genetically heterogeneous neuromuscular disorder and one of the most common congenital myopathies. The clinical manifestations usually vary depending on the age of onset. Neonatal nemaline myopathy has the worst prognosis, primarily due to respiratory failure. Several genes associated with nemaline myopathy have been identified, including NEB, ACTA1, TPM3, TPM2, TNNT1, CFL2, KBTBD13, KLHL40, KLHL41, LMOD3, and KBTBD13. Here, we report a neonatal Korean female patient with nemaline myopathy carrying compound heterozygous mutations in the gene KLHL40 as revealed using next generation sequencing (NGS). The patient presented with postnatal cyanosis, respiratory failure, dysphagia, and hypotonia just after birth. To identify the genetic cause underlying the neonatal myopathy, NGS-based gene panel sequencing was performed. Compound heterozygous pathogenic variants were detected in KLHL40: c.[1405G>T];[1582G>A] (p. [Gly469cys];[Glu528Lys]). NGS allows quick and accurate diagnosis at a lower cost compared to traditional serial single gene sequencing, which is greatly advantageous in genetically heterogeneous disorders such as myopathies. Rapid diagnosis will facilitate efficient and timely genetic counseling, prediction of disease prognosis, and establishment of treatments.

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References

  1. Lee JM, Lim JG, Shin JH, Park YE, Kim DS. Clinical and genetic diversity of nemaline myopathy from a single neuromuscular center in Korea. J Neurol Sci 2017;383:61-8. https://doi.org/10.1016/j.jns.2017.10.020
  2. Moreau-Le Lan S, Aller E, Calabria I, Gonzalez-Tarancon L, Cardona-Gay C, Martinez-Matilla M, et al. New mutations found by next-generation sequencing screening of Spanish patients with nemaline myopathy. PLoS One 2018;13:e0207296. https://doi.org/10.1371/journal.pone.0207296
  3. Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST, et al. Nemaline myopathy: a clinical study of 143 cases. Ann Neurol 2001;50:312-20. https://doi.org/10.1002/ana.1080
  4. Romero NB, Sandaradura SA, Clarke NF. Recent advances in nemaline myopathy. Curr Opin Neurol 2013;26:519-26. https://doi.org/10.1097/WCO.0b013e328364d681
  5. Wallgren-Pettersson C, Lehtokari VL, Kalimo H, Paetau A, Nuutinen E, Hackman P, et al. Distal myopathy caused by homozygous missense mutations in the nebulin gene. Brain 2007;130 (Pt 6):1465-76. https://doi.org/10.1093/brain/awm094
  6. Ravenscroft G, Miyatake S, Lehtokari VL, Todd EJ, Vornanen P, Yau KS, et al. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. Am J Hum Genet 2013;93:6-18. https://doi.org/10.1016/j.ajhg.2013.05.004
  7. Wang Q, Hu Z, Chang X, Yu M, Xie Z, Lv H, et al. Mutational and clinical spectrum in a cohort of Chinese patients with hereditary nemaline myopathy. Clin Genet 2020;97:878-89. https://doi.org/10.1111/cge.13745
  8. Kawase K, Nishino I, Sugimoto M, Togawa T, Sugiura T, Kouwaki M, et al. Nemaline myopathy with KLHL40 mutation presenting as congenital totally locked-in state. Brain Dev 2015;37:887-90. https://doi.org/10.1016/j.braindev.2015.02.002
  9. Park YE, Shin JH, Kim HS, Lee CH, Kim DS. Characterization of congenital myopathies at a Korean neuromuscular center. Muscle Nerve 2018;58:235-44. https://doi.org/10.1002/mus.26147
  10. Piga D, Magri F, Ronchi D, Corti S, Cassandrini D, Mercuri E, et al. New mutations in NEB gene discovered by targeted next-generation sequencing in nemaline myopathy Italian patients. J Mol Neurosci 2016;59:351-9. https://doi.org/10.1007/s12031-016-0739-2
  11. Avasthi KK, Agarwal S, Panigrahi I. KLHL40 mutation associated with severe nemaline myopathy, fetal akinesia, and cleft palate. J Pediatr Neurosci 2019;14:222-4. https://doi.org/10.4103/jpn.JPN_60_19
  12. Haliloglu G. Nemaline rod myopathy. In: Robert MK, Joseph WST, Nathan JB, Samir SS, Robert CT, Karen MW, editors. Nelson textbook of pediatrics. 21st ed. Philadelphia: Elsevier, 2020:3264-6.