Berta Estévez-Arias, Leslie Matalonga, Loreto Martorell, Anna Codina, Carlos Ortez, Laura Carrera-García, Jessica Expósito-Escudero, Delia Yubero, Janet Hoenicka, Cristina Jou, Francesc Palau, Sergi Beltran, Hanns Lochmüller, Ana Töpf, Andrés Nascimento, Daniel Natera-de Benito
Congenital myopathies (CMs) are rare genetic disorders for which the diagnostic yield does not typically exceed 60% . We performed deep phenotyping, histopathological studies, clinical exome and trio genome sequencing and a phenotype-driven analysis of the genomic data, that led to the molecular diagnosis in a child with CM. We identified a heterozygous variant in RYR1 in the affected child, inherited from her asymptomatic mother. Given the alignment of the clinical and histopathological phenotype with RYR1-CM, we considered the potential existence of a missing second variant in trans in the proband, but also hypothesized that the variant might be mosaic in the mother, as subsequently demonstrated...
March 10, 2024: Journal of Neuromuscular Diseases