Novel RPL13 Variants and Variable Clinical Expressivity in a Human Ribosomopathy With Spondyloepimetaphyseal Dysplasia

Autor: Outi Mäkitie, Gen Nishimura, Yves Sznajer, Valérie Cormier-Daire, Francesca Tonelli, Tuomas Näreoja, Yong Uk Kwon, Anh Nhi Tran, Valentina Daponte, Ok Hwa Kim, Helena Valta, Tae Joon Cho, Alan J. Warren, Jung Yun Bae, Antonella Forlino, Alice Costantini, Nadi Kirova, Jessica J. Alm, Woo Yeong Chung, Shengjiang Tan, Céline Huber
Přispěvatelé: UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Centre de référence neuromusculaire, UCL - SSS/IREC/SLUC - Pôle St.-Luc, HUS Children and Adolescents, Children's Hospital, University of Helsinki, Helsinki University Hospital Area, Clinicum, Lastentautien yksikkö, CAMM - Research Program for Clinical and Molecular Metabolism, Research Programs Unit
Rok vydání: 2020
Předmět:
0301 basic medicine
WEB TOOL
Ribosomopathy
Endocrinology
Diabetes and Metabolism
0302 clinical medicine
Missense mutation
Orthopedics and Sports Medicine
ENCODES
Zebrafish
Genetics
CHOPCHOP
Phenotype
Penetrance
Neoplasm Proteins
Pedigree
3. Good health
CRISPR-CAS9
Original Article
medicine.symptom
Ribosomal Proteins
030209 endocrinology & metabolism
Biology
Osteochondrodysplasias
Short stature
RPL13
03 medical and health sciences
SKELETAL
Spondyloepimetaphyseal dysplasia
Variable expressivity
INCOMPLETE PENETRANCE
medicine
Animals
Humans
Incomplete penetrance
MUTATIONS
SPONDYLOEPIMETAPHYSEAL DYSPLASIA
ZEBRAFISH
RIBOSOMOPATHY
Original Articles
medicine.disease
biology.organism_classification
GENE
Spine
030104 developmental biology
Biological Variation
Population
VARIABLE EXPRESSIVITY
Dysplasia
3121 General medicine
internal medicine and other clinical medicine
CRISPR‐CAS9
Zdroj: Journal of Bone and Mineral Research
Journal of bone and mineral research, Vol. 36, no. 2, p. 283-297 (2021)
ISSN: 1523-4681
0884-0431
Popis: Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant in RPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation‐positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia. In vitro studies on patient‐derived dermal fibroblasts harboring RPL13 missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p
Databáze: OpenAIRE
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