A Korean Case of Neonatal Nemaline Myopathy Carrying KLHL40 Mutations Diagnosed Using Next Generation Sequencing
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (12)
- Lee JM, "Clinical and genetic diversity of nemaline myopathy from a single neuromuscular center in Korea", J Neurol Sci, 383, pp.61~68 (2017)
- Moreau-Le Lan S, "New mutations found by next-generation sequencing screening of Spanish patients with nemaline myopathy", PLoS One, 13, pp.e0207296~ (2018)
- Ryan MM, "Nemaline myopathy : a clinical study of 143cases", Ann Neurol, 50, pp.312~320 (2001)
- Romero NB, "Recent advances in nemaline myopathy", Curr Opin Neurol, 26, pp.519~526 (2013)
- Wallgren-Pettersson C, "Distal myopathy caused by homozygous missense mutations in the nebulin gene", Brain, 130(Pt 6), pp.1465~1476 (2007)
- Ravenscroft G, "Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy", Am J Hum Genet, 93, pp.6~18 (2013)
- Wang Q, "Mutational and clinical spectrum in a cohort of Chinese patients with hereditary nemaline myopathy", Clin Genet, 97, pp.878~889 (2020)
- Kawase K, "Nemaline myopathy with KLHL40 mutation presenting as congenital totally locked-in state", Brain Dev, 37, pp.887~890 (2015)
- Park YE, "Characterization of congenital myopathies at a Korean neuromuscular center", Muscle Nerve, 58, pp.235~244 (2018)
- Piga D, "New mutations in NEB gene discovered by targeted nextgeneration sequencing in nemaline myopathy Italian patients", J Mol Neurosci, 59, pp.351~359 (2016)
- Avasthi KK, "KLHL40 mutation associated with severe nemaline myopathy, fetal akinesia, and cleft palate", J Pediatr Neurosci, 14, pp.222~224 (2019)
- Haliloglu G, "Nelson textbook of pediatrics", pp.3264~3266 (2020), Elsevier