Evolution of clinical and radiological presentations of spondyloepimetaphyseal dysplasia, RPL13-related: Description of 11 further cases.

Francisca Díaz-González, Manuel Parrón-Pajares, Elsa Lucas-Castro, Silvia Modamio-Høybjør, Lucia Sentchordi-Montané, Verónica Seidel, Pablo Prieto, Guillermo Tarraso-Urios, Marta Codina-Sola, Anna M Cueto-González, Mary J Ballesta-Martínez, Fernando Santos-Simarro, Sergio B Sousa, Karen E Heath

Journal: Clinical genetics 2023;104(1):100-106

PMID: 37121912

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Abstract

Spondyloepimetaphyseal dysplasia (SEMD), RPL13-related is caused by heterozygous variants in RPL13, which encodes the ribosomal protein eL13, a component of the 60S human ribosomal subunit. Here, we describe the clinical and radiological evolution of 11 individuals, 7 children and 4 adults, from 6 families. Some of the skeletal features improved during the course of this condition, whilst others worsened. We describe for the first time "corner fractures" as a feature of this dysplasia which as with other dysplasias disappear with age. In addition, we review the heights and skeletal anomalies of these reported here and previously in a total of 25 individuals from 15 families. In this study, six different RPL13 variants were identified, five of which were novel. All were located in the apparently hotspot region, located in intron 5 and exon 6. Splicing assays were performed for two of the three previously undescribed splicing variants. Until now, all splice variants have occurred in the intron 5 splice donor site, incorporating an additional 18 amino acids to the mutant protein. Here, we report the first variant in intron 5 splice acceptor site which generates two aberrant transcripts, deleting the first three and four amino acids encoded by exon 6. Thus, this study doubles the number of SEMD-RPL13-related cases and variants reported to date and describes unreported age-related clinical and radiological features.

Address: Institute of Medical & Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario la Paz, UMA, Madrid, Spain.; Skeletal dysplasia multidisciplinary Unit (UMDE), Hospital Universitario la Paz, Madrid, Spain.; European Research Network on Rare BONe Disorders (ERN-BOND).; Skeletal dysplasia multidisciplinary Unit (UMDE), Hospital Universitario la Paz, Madrid, Spain.; European Research Network on Rare BONe Disorders (ERN-BOND).; Department of Radiology, Hospital Universitario La Paz, Madrid, Spain.; Department of Pediatrics, Hospital Universitario Infanta Leonor, Madrid, Spain.; Department of Pediatrics, Universidad Complutense, Madrid, Spain.; Clinical Genetics Section, Department of Pediatrics, Hospital Universitario Gregorio Marañón, Madrid, Spain.; Department of Pediatrics, Hospital Universitario Clínico Salamanca and Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain.; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; Medical Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; European Research Network on Rare BONe Disorders (ERN-BOND).; Department of Clinical and Molecular Genetics, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; Medical Genetics Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; European Research Network on Rare BONe Disorders (ERN-BOND).; Medical Genetics Section, Department of Pediatrics, Hospital Universitario Virgen de la Arrixaca, IMIB, Murcia, Spain.; CIBERER, ISCIII, Madrid, Spain.; Institute of Medical & Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario la Paz, UMA, Madrid, Spain.; Skeletal dysplasia multidisciplinary Unit (UMDE), Hospital Universitario la Paz, Madrid, Spain.; European Research Network on Rare BONe Disorders (ERN-BOND).; CIBERER, ISCIII, Madrid, Spain.; Department of Molecular diagnostics & Clinical Genetics, Hospital Universitario Son Espases, Palma, Mallorca, Spain.; European Research Network on Rare BONe Disorders (ERN-BOND).; Medical Genetics Unit, Hospital Pediátrico, Centro Hospitalar & Universitário de Coimbra, Coimbra, Portugal.; Institute of Medical & Molecular Genetics (INGEMM), IdiPAZ, Hospital Universitario la Paz, UMA, Madrid, Spain.; Skeletal dysplasia multidisciplinary Unit (UMDE), Hospital Universitario la Paz, Madrid, Spain.; European Research Network on Rare BONe Disorders (ERN-BOND).; CIBERER, ISCIII, Madrid, Spain.

DOI: 10.1111/cge.14351

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MeSH Terms: Child, Adult, Humans, Ribosomal Proteins, Osteochondrodysplasias, Radiography, Exons, Amino Acids, Neoplasm Proteins