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Haploinsufficiency of MEIS2 is associated with orofacial clefting and learning disability
Author(s) -
Johansson Stefan,
Berland Siren,
Gradek Gyri Aasland,
Bongers Ernie,
de Leeuw Nicole,
Pfundt Rolph,
Fannemel Madeleine,
Rødningen Olaug,
Brendehaug Atle,
Haukanes Bjørn Ivar,
Hovland Randi,
Helland Gunnar,
Houge Gunnar
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36498
Subject(s) - haploinsufficiency , intellectual disability , short stature , medicine , genetics , biology , pediatrics , gene , phenotype
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. © 2014 Wiley Periodicals, Inc.