Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Berghold, VM; Koko, M; Berutti, R; Plecko, B.
Case report: Novel SCN4A variant associated with a severe congenital myasthenic syndrome/myopathy phenotype.
Front Pediatr. 2022; 10: 944784
Doi: 10.3389/fped.2022.944784
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- Führende Autor*innen der Med Uni Graz
- Berghold Veronika Marlies
- Plecko Barbara
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- Abstract:
- We present a now 18-year-old female patient with a severe congenital myopathy phenotype, originally diagnosed as mitochondrial myopathy, however later revealed to constitute a SCN4A-related myopathy based on genetic testing. After birth, floppiness, bradycardia and respiratory insufficiency ensued, and moderately reduced mitochondrial complex I activity was found in muscle tissue (tested at 3 weeks and 3 years of age, respectively). She was treated with riboflavin, carnitine, creatine and a ketogenic diet. At the age of 13 years, whole exome sequencing challenged the initial diagnosis by identifying two (compound heterozygous) SCN4A variants affecting the highly conserved voltage sensor and pore regions of the voltage-gated sodium channel NaV1.4: a known pathogenic loss of function (LOF) variant [c.4360C>T; p.(Arg1454Trp)] and a novel variant of uncertain significance [c.3615C>G; p.(Asn1205Lys)]. For this novel variant, a LOF effect was predicted by in silico, clinical and functional evidence from paralog human sodium channels, and the variant was accordingly classified as likely pathogenic. The patient's phenotype is in line with the few published cases of autosomal recessive SCN4A-related myopathy. There was limited benefit from treatment with salbutamol and acetazolamide, while pyridostigmine caused side effects at a minor dose. This report highlights the importance of genetic testing in severe myopathies particularly in regard to treatment options and the value of paralog information in evaluating ion channel variations.
- Find related publications in this database (Keywords)
- Na(V)1
- 4 voltage-gated sodium channel
- loss of function (LOF)
- ion channel gene defect
- whole exome sequencing
- ion channels
- sodium channel paralogs
- genetic testing
- complex I deficiency