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Verheije, R.* ; Kupchik, G.S.* ; Isidor, B.* ; Kroes, H.Y.* ; Lynch, S.A.* ; Hawkes, L.* ; Hempel, M.* ; Gelb, B.D.* ; Ghoumid, J.* ; D’Amours, G.* ; Chandler, K.* ; Dubourg, C.* ; Loddo, S.* ; Tümer, Z.* ; Shaw-Smith, C.* ; Nizon, M.* ; Shevell, M.* ; Van Hoof, E.* ; Anyane-Yeboa, K.* ; Cerbone, G.* ; Clayton-Smith, J.* ; Cogné, B.* ; Corre, P.* ; Corveleyn, A.* ; De Borre, M.* ; Hjortshøj, T.D.* ; Fradin, M.* ; Gewillig, M.* ; Goldmuntz, E.* ; Hens, G.* ; Lemyre, E.* ; Journel, H.* ; Kini, U.* ; Kortüm, F.* ; Le Caignec, C.* ; Novelli, A.* ; Odent, S.* ; Petit, F.* ; Revah-Politi, A.* ; Stong, N.* ; Strom, T.M. ; van Binsbergen, E.* ; DDD Study* ; Devriendt, K.* ; Breckpot, J.*

Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability.

Eur. J. Hum. Genet. 27, 278-290 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype-phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords De-novo Mutations; Cleft-palate; Cardiac Development; Deletion; Foxp1; 15q14; Haploinsufficiency; Zebrafish; Genes; Xiap
ISSN (print) / ISBN 1018-4813
e-ISSN 1476-5438
Journal European Journal of Human Genetics
Quellenangaben Volume: 27, Issue: 2, Pages: 278-290 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Macmillan Building, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)