title: Haploinsufficiency of MEIS2 is associated with orofacial clefting and learning disability.
abstract: MEIS2 is a homeodomain-containing transcription factor of the TALE superfamily that has been proven important for development. We confirm and extend a recent single clinical report stating that deletions in MEIS2 can cause cleft palate [Crowley et al. (2010); Am J Med Genet 152A:1326-1327]. Here we report on five additional patients with 15q14 deletions of sizes 0.6, 0.6, 1.0, 1.9, and 4.8 Mb, respectively, all involving MEIS2. In addition, we present a family with four affected individuals and an intragenic 58 kb direct duplication disrupting MEIS2. In total, 7/9 cases had clefting, from mild (submucous cleft palate) to severe (cleft lip and palate), and 3/9 cases had ventricular septal defects. All cases had delayed motor development and most had learning disability, at worst in the mild intellectual disability range. The cases had overlapping facial features (broad forehead, finely arched eyebrows, mildly shortened philtrum, and tented upper lip) but individually they were not considered to be dysmorphic. Our results show that MEIS2 is a gene needed for palate closure. In syndromic cases of cleft palate, MEIS2 should be considered among the candidate genes, for example, in cases without 22q11.2 deletions.
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Stefan
authors.initials: S
authors.lastname: Johansson
authors.forename: Siren
authors.initials: S
authors.lastname: Berland
authors.forename: Gyri Aasland
authors.initials: GA
authors.lastname: Gradek
authors.forename: Ernie
authors.initials: E
authors.lastname: Bongers
authors.forename: Nicole
authors.initials: N
authors.lastname: de Leeuw
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: Madeleine
authors.initials: M
authors.lastname: Fannemel
authors.forename: Olaug
authors.initials: O
authors.lastname: Rødningen
authors.forename: Atle
authors.initials: A
authors.lastname: Brendehaug
authors.forename: Bjørn Ivar
authors.initials: BI
authors.lastname: Haukanes
authors.forename: Randi
authors.initials: R
authors.lastname: Hovland
authors.forename: Gunnar
authors.initials: G
authors.lastname: Helland
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houge
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002971:Cleft Lip / Q000175:diagnosis / Q000235:genetics*; D002972:Cleft Palate / Q000175:diagnosis / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D057895:Haploinsufficiency; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007859:Learning Disabilities / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C491172:MEIS2 protein, human; D014157:Transcription Factors
keywords: MEIS2; cleft lip; cleft palate; intellectual disability