2. Academic Validation
  3. VPS51 biallelic variants cause microcephaly with brain malformations: A confirmatory report

VPS51 biallelic variants cause microcephaly with brain malformations: A confirmatory report

  • Eur J Med Genet. 2019 Aug;62(8):103704. doi: 10.1016/j.ejmg.2019.103704.
Annette Uwineza 1,  Jean-Hubert Caberg 2,  Janvier Hitayezu 3,  Stephane Wenric 4,  Leon Mutesa 3,  Yoann Vial 5,  Séverine Drunat 5,  Sandrine Passemard 5,  Alain Verloes 5,  Vincent El Ghouzzi 6,  Vincent Bours 2
Affiliations

Affiliations

  • 1 Center for Human Genetics, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda. Electronic address: A.UWINEZA@ur.ac.rw.
  • 2 Center for Human Genetics, Centre Hospitalier Universitaire, University of Liege, Liege, Belgium.
  • 3 Center for Human Genetics, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
  • 4 GIGA-Research, Human Genetics Unit, University of Liege, Liege, Belgium.
  • 5 Department of Genetics, AP HP - Robert Debré University Hospital, Paris, France; PROTECT, INSERM UMR1141, Université de Paris, Paris, France.
  • 6 PROTECT, INSERM UMR1141, Université de Paris, Paris, France.
PMID: 31207318 DOI: 10.1016/j.ejmg.2019.103704
Abstract

Whole exome Sequencing undertaken in two siblings with delayed psychomotor development, absent speech, severe intellectual disability and postnatal microcephaly, with brain malformations consisting of cerebellar atrophy in the eldest affected and hypoplastic corpus callosum in the younger sister; revealed a homozygous intragenic deletion in VPS51, which encodes the vacuolar protein sorting-associated protein, one the four subunits of the Golgi-associated retrograde protein (GARP) and endosome-associated recycling protein (EARP) complexes that promotes the fusion of endosome-derived vesicles with the trans-Golgi network (GARP) and recycling endosomes (EARP). This observation supports a pathogenic effect of VPS51 variants, which has only been reported previously once, in a single child with microcephaly. It confirms the key role of membrane trafficking in normal brain development and homeostasis.

Keywords

EARP; Endosomes; GARP; Golgi; Golgipathies; Neurodevelopmental disorders; Postnatal microcephaly; Rwanda; VPS51.

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