2. Academic Validation
  3. Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay

Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay

  • Eur J Hum Genet. 2017 Aug;25(8):946-951. doi: 10.1038/ejhg.2017.86.
Karin Weiss 1,  Kristen Wigby 2 3,  Madeleine Fannemel 4,  Lindsay B Henderson 5,  Natalie Beck 6,  Neeti Ghali 7,  D D D Study 8,  Britt-Marie Anderlid 9,  Johanna Lundin 9,  Ada Hamosh 6,  Marilyn C Jones 2 3,  Sondhya Ghedia 10,  Maximilian Muenke 1,  Paul Kruszka 1
Affiliations

Affiliations

  • 1 Department of Medical Genetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • 2 Department of Pediatrics, University of California, San Diego, CA, USA.
  • 3 Rady Children's Hospital, San Diego, CA, USA.
  • 4 Department of Medical Genetics, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
  • 5 GeneDx, Gaithersburg, MD, USA.
  • 6 Department of Pediatrics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 7 North West Thames Regional Genetics Service, Northwick Park Hospital, London North West Healthcare NHS Trust, Harrow, UK.
  • 8 DDD Study, Wellcome Trust Sanger Institute, Cambridge, UK.
  • 9 Department of Molecular Medicine and Surgery, Centre of Molecular Medicine, Karoliniska Institutet and Clincal Genetics, Karolinska University Hospital, Stockholm, Sweden.
  • 10 The Department of Clinical Genetics, Royal North Shore Hospital, Pacific Highway, St Leonards, New South Wales, Australia.
PMID: 28513610 DOI: 10.1038/ejhg.2017.86
Abstract

The introduction of whole-exome Sequencing into the Pediatric Genetics clinic has increased the identification of novel genes associated with neurodevelopmental disorders and congenital anomalies. This agnostic approach has shed LIGHT on multiple proteins and pathways not previously known to be associated with disease. Here we report eight subjects from six families with predicted loss of function variants in ZNF462, a zinc-finger protein of unknown function. These individuals have overlapping phenotypes that include ptosis, metopic ridging, craniosynostosis, dysgenesis of the corpus callosum, and developmental delay. We propose that ZNF462 plays an important role in embryonic development, and is associated with craniofacial and neurodevelopmental abnormalities.

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