Core myopathy in two siblings with a biallelic variant in the CACNA1S gene-A case series study.
Tara KhoeiniAriana KariminejadYalda NilipourArmin AriaeiHossein NajmabadiMojtaba ArabshahiMehrshid Faraji ZonoozBahram Haghi AshtianiPublished in: Clinical case reports (2024)
Calcium Voltage-Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation has been linked to various neuromuscular conditions in recent years. Congenital myopathy with core-like features is one of the cardinal associations reported previously, causing severe respiratory insufficiency and death in neonates. Informed consent was received from the patients. Subsequently, peripheral blood leukocytes were utilized to extract genomic DNA. Moreover, exome enrichment was implemented through the Twist Human Core Exome Kit (Twist Bioscience) and exome sequenced using Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Sanger sequencing using BIG Dye Terminators confirmed the presence of the final variant. Finally, the candidate variants were classified based on the American College of Medical Genetics and Genomics (ACMG) guidelines. In this report, we describe two siblings, who presented with childhood and late-onset progressive muscle weakness, and had a homozygous variant in exon 2 of the CACNA1S gene defined as c.188C > A (p.Ala63Asp) (NM_000069.3). The SIFT, Polyphen2, CADD PHRED, and Mutation Taster analysis tools classified the variant as pathogenic/damaging. The muscle biopsy of the younger brother revealed intermyofibrillar network pattern disruption as cytoplasmic core-like lesions. The muscle magnetic resonance imaging (MRI) reported grade IIa and IIb fatty changes. Finally, the electromyography (EMG) findings suggested a myopathic change pattern. This report illustrates the clinical variability in CACNA1S-related myopathy by reviewing prior reports and adding newly found aspects, additionally expanding the gene defects associated with core myopathy.
Keyphrases
- late onset
- copy number
- early onset
- magnetic resonance imaging
- peripheral blood
- genome wide
- end stage renal disease
- skeletal muscle
- single cell
- chronic kidney disease
- intellectual disability
- epithelial mesenchymal transition
- healthcare
- contrast enhanced
- dna methylation
- ejection fraction
- autism spectrum disorder
- peritoneal dialysis
- oxidative stress
- newly diagnosed
- genome wide identification
- high throughput
- emergency department
- muscular dystrophy
- magnetic resonance
- cell free
- preterm infants
- prognostic factors
- fatty acid
- anti inflammatory
- protein kinase
- early life
- machine learning
- high throughput sequencing