Common genetic causes of holoprosencephaly are limited to a small set of evolutionarily conserved driver genes of midline development coordinated by TGF-β, hedgehog, and FGF signaling.

Author(s): Roessler E,  Hu P,  Marino J,  Hong S,  Hart R,  Berger S,  Martinez A,  Abe Y,  Kruszka P,  Thomas JW,  Mullikin JC,  NISC Comparative Sequencing Program,  Wang Y,  Wong WSW,  Niederhuber JE,  Solomon BD,  Richieri-Costa A,  Ribeiro-Bicudo LA,  Muenke M

Journal: Hum Mutat

Date: 2018 Oct

Major Program(s) or Research Group(s): BRG

PubMed ID: 29992659

PMC ID: not available

Abstract: Here, we applied targeted capture to examine 153 genes representative of all the major vertebrate developmental pathways among 333 probands to rank their relative significance as causes for holoprosencephaly (HPE). We now show that comparisons of variant transmission versus nontransmission among 136 HPE Trios indicates some reported genes now lack confirmation, while novel genes are implicated. Furthermore, we demonstrate that variation of modest intrinsic effect can synergize with these driver mutations as gene modifiers.