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Hum Mutat. 2015 Dec;36(12):1155-8. doi: 10.1002/humu.22860. Epub 2015 Sep 14.

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

Author information

1
Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRRCS, Rome, Italy.
2
Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
3
Department of Cell Biology, University of Salzburg, Salzburg, Austria.
4
Unit of Child Neuropsychiatry, Department of Neurosciences, Bambino Gesù Children's Hospital, IRRCS, Rome, Italy.
5
Unit of Neurology, Department of Neurosciences, Bambino Gesù Children's Hospital, IRRCS, Rome, Italy.
6
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
7
Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
8
Research Laboratories, Bambino Gesù Children's Hospital, IRRCS, Rome, Italy.
9
Unit of Nephrology, Department of Pediatrics, Bambino Gesù Children's Hospital, IRRCS, Rome, Italy.
10
Unit of Clinical Endocrinology, Department of Pediatrics, Bambino Gesù Children's Hospital, IRRCS, Rome, Italy.

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.

KEYWORDS:

RPL10; XLID; cerebellar hypoplasia; spondylo-epiphyseal dysplasia; uL16

PMID:
26290468
DOI:
10.1002/humu.22860
[Indexed for MEDLINE]

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