Neonatal Med.  2021 May;28(2):89-93. 10.5385/nm.2021.28.2.89.

A Korean Case of Neonatal Nemaline Myopathy Carrying KLHL40 Mutations Diagnosed Using Next Generation Sequencing

• Suh Ya
• Sohn YB
• Park MS
• Lee JH

• KMID: 2516491
• DOI: http://doi.org/10.5385/nm.2021.28.2.89

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.

Keyword

Congenital; Myopathies, nemaline; Next generation sequencing; KLHL40

Figure

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  Figure 1. Chest X-ray taken at the time of admission of the patient to our hospital revealed no abnormal findings except cardiomegaly.

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  Figure 2. Chest X-ray taken at hospital day 2, revealed aggravated haziness in both lungs; therefore, the patient was intubated.

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  Figure 3. Next generation sequencing analysis showing compound heterozygous mutations in the gene KLHL40: KLHL40 c.[1405G>T];[1582G>A] (p.[Gly469cys];[Glu528Lys]).

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