Key result
Combining next-generation sequencing and multiplex ligation-dependent probe amplification identified a known missense mutation (p.G482R) and a novel deletion of the last 3 exons in the CLCN1 gene.
Case Report (n=1)
Combining multiple genetic techniques such as NGS and MLPA is crucial for accurately defining recessive forms of myotonia congenita by identifying both point mutations and exon deletions.
May support combined NGS-MLPA testing for recessive myotonia congenita diagnosis; leaves open validation in larger cohorts.
Myotonia congenita (MC) is a hereditary skeletal muscle disorder characterized by muscle stiffness at the beginning of exercise (i.e. myotonia), alleviated by repetition of contraction (ie. warm-up effect). MC is caused by mutations in the CLCN1 gene, encoding the skeletal muscle voltage-gated chloride channel (ClC-1) and is traditionally classified as Thomsen (autosomal dominant) and Becker (autosomal recessive) diseases. We report here an Italian patient affected by diffuse muscle hypertrophy, predominant in lower limb, neck, and trapezius and difficulty in getting up from a chair after prolonged rest, suggestive of recessive MC. The combination of a specific next-generation sequencing panel for skeletal muscle channelopathies and multiplex ligation-dependent probe amplification for CLCN1 , leaded to the detection of the known missense mutation p.G482R and a novel deletion of the last 3 exons of the CLCN1 . This report demonstrates the importance of combining multiple genetic techniques to define recessive forms of MC.
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Brugnoni et al. (2024) conducted a case report in Recessive myotonia congenita (n=1). Next-generation sequencing (NGS) combined with multiplex ligation-dependent probe amplification (MLPA) was evaluated on Detection of pathogenic variants in the CLCN1 gene. Combining next-generation sequencing and multiplex ligation-dependent probe amplification identified a known missense mutation (p.G482R) and a novel deletion of the last 3 exons in the CLCN1 gene.
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