2. Academic Validation
  3. Biallelic loss-of-function variants in RBL2 in siblings with a neurodevelopmental disorder

Biallelic loss-of-function variants in RBL2 in siblings with a neurodevelopmental disorder

  • Ann Clin Transl Neurol. 2020 Mar;7(3):390-396. doi: 10.1002/acn3.50992.
Theresa Brunet 1 2,  Milena Radivojkov-Blagojevic 2,  Peter Lichtner 2,  Verena Kraus 3,  Thomas Meitinger 1 2,  Matias Wagner 1 2 4
Affiliations

Affiliations

  • 1 Institute of Human Genetics, Faculty of Medicine, Technical University Munich, Munich, Germany.
  • 2 Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
  • 3 Department of Pediatrics, Klinik für Kinder- und Jugendmedizin, München Klinik Schwabing und Harlaching, Klinikum Rechts der Isar der Technischen Universität Munich, Munich, Germany.
  • 4 Institute for Neurogenomics, Helmholtz Zentrum München, Neuherberg, Germany.
PMID: 32105419 DOI: 10.1002/acn3.50992
Abstract

The RBL2 locus has been associated with intelligence and educational attainment but not with a monogenic disorder to date. RBL2 encodes p130, a member of the retinoblastoma protein family, which is involved in mediating neuron survival and death. Previous studies on p130 knockout mice revealing embryonic death and impaired neurogenesis underscore the importance of RBL2 in brain development. Exome sequencing in two siblings with severe intellectual disability, stereotypies and dysmorphic features identified biallelic loss-of-function variants c.556C>T, p.(Arg186Ter) and a deletion of exon 13-17 in RBL2 (NM_005611.3), establishing RBL2 as a candidate gene for an autosomal recessive neurodevelopmental disorder.

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