Holoprosencephaly in the genomics era. Issue 2 (17th May 2018)

• Record Type: Journal Article
• Authors: Roessler, Erich; Hu, Ping; Muenke, Maximilian
• Other Names: Kruszka Paul S. guestEditor.; Solomon Benjamin D. guestEditor.; Muenke Maximilian guestEditor.
• Is Part Of: American journal of medical genetics. Volume 178:Issue 2(2018)
• Page Start: 165
• Page End: 174
• Publication Date: 2018-05-17
• Subjects: environmental modifier -- gene driver -- gene modifier -- HPE -- multifactorial inheritance; Medical genetics -- Periodicals; 616.04205
• DOI: 10.1002/ajmg.c.31615
• Languages: English
• ISSNs: 1552-4868

Abstract

Abstract : Holoprosencephaly (HPE) is the direct consequence of specific genetic and/or environmental insults interrupting the midline specification of the nascent forebrain. Such disturbances can lead to a broad range of phenotypic consequences for the brain and face in humans. This malformation sequence is remarkably common in utero (1 in 250 human fetuses), but 97% typically do not survive to birth. The precise molecular pathogenesis of HPE in these early human embryos remains largely unknown. Here, we outline our current understanding of the principal driving factors leading to HPE pathologies and elaborate our multifactorial integrated genomics approach. Overall, our understanding of the pathogenesis continues to become simpler, rather than more complicated. Genomic technologies now provide unprecedented insight into disease‐associated variation, including the overall extent of genetic interactions (coding and noncoding) predicted to explain divergent phenotypes.