A Novel Mutation in RPL10 (Ribosomal Protein L10) Causes X-Linked Intellectual Disability, Cerebellar Hypoplasia, and Spondylo-Epiphyseal Dysplasia

Ginevra Zanni, Vera M. Kalscheuer, Andreas Friedrich, Sabina Barresi, Paolo Alfieri, Matteo Di Capua, Stefan A. Haas, Giorgia Piccini, Thomas Karl, Sabine M. Klauck, Emanuele Bellacchio, Francesco Emma, Marco Cappa, Enrico Bertini, Lore Breitenbach-Koller

Research output: Contribution to journalArticle

Abstract

RPL10 encodes ribosomal protein L10 (uL16), a highly conserved multifunctional component of the large ribosomal subunit, involved in ribosome biogenesis and function. Using X-exome resequencing, we identified a novel missense mutation (c.191C>T; p.(A64V)) in the N-terminal domain of the protein, in a family with two affected cousins presenting with X-linked intellectual disability, cerebellar hypoplasia, and spondylo-epiphyseal dysplasia (SED). We assessed the impact of the mutation on the translational capacity of the cell using yeast as model system. The mutation generates a functional ribosomal protein, able to complement the translational defects of a conditional lethal mutation of yeast rpl10. However, unlike previously reported mutations, this novel RPL10 missense mutation results in an increase in the actively translating ribosome population. Our results expand the mutational and clinical spectrum of RPL10 identifying a new genetic cause of SED and highlight the emerging role of ribosomal proteins in the pathogenesis of neurodevelopmental disorders.

Original languageEnglish
Pages (from-to)1155-1158
Number of pages4
JournalHuman Mutation
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 1 2015

Fingerprint

Intellectual Disability
Mutation
Ribosomal Proteins
Missense Mutation
Ribosomes
Yeasts
Large Ribosome Subunits
Exome
ribosomal protein L10
Cerebellar Hypoplasia
Population

Keywords

  • Cerebellar hypoplasia
  • RPL10
  • Spondylo-epiphyseal dysplasia
  • UL16
  • XLID

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A Novel Mutation in RPL10 (Ribosomal Protein L10) Causes X-Linked Intellectual Disability, Cerebellar Hypoplasia, and Spondylo-Epiphyseal Dysplasia. / Zanni, Ginevra; Kalscheuer, Vera M.; Friedrich, Andreas; Barresi, Sabina; Alfieri, Paolo; Di Capua, Matteo; Haas, Stefan A.; Piccini, Giorgia; Karl, Thomas; Klauck, Sabine M.; Bellacchio, Emanuele; Emma, Francesco; Cappa, Marco; Bertini, Enrico; Breitenbach-Koller, Lore.

In: Human Mutation, Vol. 36, No. 12, 01.12.2015, p. 1155-1158.

Research output: Contribution to journalArticle

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