biostudies-literatureJanßen SDeutsche ForschungsgemeinschaftDr. Georg E. und Marianne Kosing-Stiftung10867https://www.ebi.ac.uk/biostudies/studies/S-EPMC11477233biostudies-literatureUnknown25(19)Pathogenic variants in the ryanodine receptor 1 (<i>RYR1</i>) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype-phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic <i>RYR1</i> variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic <i>RYR1</i> variant that has recently been described in another patient with severe congenital myopathy and International journal of molecular sciencesCompound Heterozygous &lt;i&gt;RYR1&lt;/i&gt; Variants in a Patient with Severe Congenital Myopathy: Case Report and Comparison with Additional Cases of Recessive &lt;i&gt;RYR1&lt;/i&gt;-Related Myopathy.PMC11477233no numberDoring KLubieniecka JMLubieniecki KPHoffjan SLucke TNguyen HHPKneifel MGuttsches AKCasadei NGerding WMJanßen SVorgerd MKohler CErbe LSHeyer CfalseCompound Heterozygous &lt;i&gt;RYR1&lt;/i&gt; Variants in a Patient with Severe Congenital Myopathy: Case Report and Comparison with Additional Cases of Recessive &lt;i&gt;RYR1&lt;/i&gt;-Related Myopathy.Pathogenic variants in the ryanodine receptor 1 (<i>RYR1</i>) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype-phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic <i>RYR1</i> variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic <i>RYR1</i> variant that has recently been described in another patient with severe congenital myopathy and 2024-01-01T00:00:00Z2024 Oct2025-04-04T13:53:58.208Z2025-04-04T13:53:58.208ZS-EPMC114772333940919710.3390/ijms251910867