Improving Diagnostic Precision: Phenotype-Driven Analysis Uncovers a Maternal Mosaicism in an Individual with RYR1-Congenital Myopathy
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 phenotypedriven analysis of the genomic data, that led to the molecular diagn...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Fundació Sant Joan de Déu |
| Repositorio: | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| OAI Identifier: | oai:fsjd.fundanetsuite.com:p25960 |
| Acceso en línea: | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=25960 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Congenital myopathy RYR1 mosaicism genome sequencing |
| Sumario: | 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 phenotypedriven 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. Our study is an example of how heterozygous variants inherited from asymptomatic parents are frequently dismissed. When the genotype-phenotype correlation is strong, it is recommended to consider a parental mosaicism. |
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