Journal article
MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis
Christopher CY Mak, Dan Doherty, Angela E Lin, Nancy Vegas, Megan T Cho, Geraldine Viot, Clemantine Dimartino, James D Weisfeld-Adams, Davor Lessel, Shelagh Joss, Chumei Li, Claudia Gonzaga-Jauregui, Yuri A Zarate, Nadja Ehmke, Denise Horn, Caitlin Troyer, Sarina G Kant, Youngha Lee, Gisele E Ishak, Gordon Leung Show all
Brain | OXFORD UNIV PRESS | Published : 2020
DOI: 10.1093/brain/awz379
Abstract
MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions encompassing MN1 have been reported in individuals with variable neurodevelopmental anomalies and non-specific facial features. We identified a cluster of de novo truncating mutations in MN1 in a cohort of 23 individuals with strikingly similar dysmorphic facial features, especially midface hypoplasia, and intellectual disability with severe expressive language delay. Imaging revealed an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar ..
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Awarded by Universite Sorbonne Paris-Cite Pole de recherche et d'enseignement superieur
Awarded by Agence Nationale de la Recherche ['Investissements d'avenir' program]
Awarded by German Research Foundation (DFG)
Awarded by NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awarded by NIH National Institute of Neurological Diseases and Stroke
Awarded by NIH National Human Genome Research Institute
Awarded by NIH National Heart, Lung and Blood Institute
Awarded by Health Innovation Challenge Fund
Funding Acknowledgements
This work was supported by grants from the Universite Sorbonne Paris-Cite Pole de recherche et d'enseignement superieur (project number SPC/JFG/2013-031), the Agence Nationale de la Recherche [CranioRespiro project and `Investissements d'avenir' program (ANR-10-IAHU-01)], MSDAvenir (DevoDecode project), E-Rare (CRANIRARE project), The Society for the Relief of Disabled Children, Medix Medical Services Asia, the Nachwuchskommission of the Charite Berlin (Rahel-Hirsch scholarship) to N.E., the German Research Foundation (DFG; SFB1315 to A.M.K. and LE 4223/1 to D.L.), the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083091, Genetics Core) to D.D., the NIH National Institute of Neurological Diseases and Stroke (R01NS050375) to W.B.D., the NIH National Human Genome Research Institute (HG009599) to J.T.S., the NIH National Human Genome Research Institute and the NIH National Heart, Lung and Blood Institute (grants UM1 HG006493 and U24 HG008956) to M.J.B. and D.A.N. (for sequencing provided by the University of Washington Center for Mendelian Genomics) and by private donations from families to D.D. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. F.R.Z. was supported by a Canadian Institute of Health Research fellowship and W.T.G. was supported by the BC Children's Hospital Research Institute through its intramural IGAP Clinician Scientist Award program. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003). This study makes use of DECIPHER (http://decipher.sanger.ac.uk), which is funded by the Wellcome. See Deciphering Developmental Disorders Study (2015) or www.ddduk.org/access.html for full acknowledgement.