RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature

Cedric Le Caignec, Benjamin Ory, François Lamoureux, Marie Francoise O'Donohue, Emilien Orgebin, Pierre Lindenbaum, Stéphane Téletchéa, Manon Saby, Anna Hurst, Katherine Nelson, Shawn R. Gilbert, Yael Wilnai, Leonid Zeitlin, Eitan Segev, Robel Tesfaye, Mathilde Nizon, Benjamin Cogne, Stéphane Bezieau, Loic Geoffroy, Antoine HamelEmmanuelle Mayrargue, Benoît de Courtivron, Aliette Decock-Giraudaud, Céline Charrier, Olivier Pichon, Christelle Retière, Richard Redon, Alexander Pepler, Kirsty McWalter, Lydie Da Costa, Annick Toutain, Pierre Emmanuel Gleizes, Marc Baud'huin*, Bertrand Isidor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Variants in genes encoding ribosomal proteins have thus far been associated with Diamond-Blackfan anemia, a rare inherited bone marrow failure, and isolated congenital asplenia. Here, we report one de novo missense variant and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13 (also called eL13), in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477+1G>T, c.477+1G>A, and c.477+2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion. In contrast to observations from Diamond-Blackfan anemia, we detected no evidence of significant pre-rRNA processing disturbance in cells derived from two affected individuals. Consistently, we showed that the insertion-containing protein is stably expressed and incorporated into 60S subunits similar to the wild-type protein. Erythroid proliferation in culture and ribosome profile on sucrose gradient are modified, suggesting a change in translation dynamics. We also provide evidence that RPL13 is present at high levels in chondrocytes and osteoblasts in mouse growth plates. Taken together, we show that the identified RPL13 variants cause a human ribosomopathy defined by a rare skeletal dysplasia, and we highlight the role of this ribosomal protein in bone development.

Original languageEnglish
Pages (from-to)1040-1047
Number of pages8
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - 7 Nov 2019
Externally publishedYes


FundersFunder number
European Diamond-Blackfan Anemia Consortium
European Research Area NetworkANR-15-RAR3-0007-04
Agence Nationale de la RechercheANR-16-CE11-0029, ANR-15-CE12-0001


    • RPL13
    • Spondyloepimetaphyseal dysplasia
    • bone dysplasia
    • chondrodysplasia
    • ribosome
    • short stature


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