title: MEIS2 involvement in cardiac development, cleft palate, and intellectual disability.
abstract: MEIS2 has been associated with cleft palate and cardiac septal defects as well as varying degrees of intellectual disability. We present a female patient with a more severe phenotype compared to previous reported patients. She has multiple congenital malformations; cleft palate and congenital heart defect characterized by septal defects and aortic coarctation. She has severe feeding problems, facial dysmorphism, severely delayed gross motor and verbal development, and autism spectrum disorder. Facial dysmorphism consisting of bitemporal narrowing, arched and laterally extended eyebrows, mild upslanting palpebral fissures, deep-set eyes, a tented upper lip, thin upper vermilion, full lower vermilion, broad first ray of hands and feet, a gap between the first and second toes, and syndactyly of toe II-III. Exome sequencing revealed a non-frameshift deletion (c.998_1000del:p.Arg333del) of three base pairs in the MEIS2 homeodomain. The more severe phenotype is most probably due to dominant-negative mechanisms. This is the first report showing a de novo small intragenic mutation in MEIS2 and further confirms the important role of this gene in normal development.
authors.affiliation: Department of Congenital and Pediatric Cardiology, University Hospitals Leuven, Belgium; Center of Human Genetics, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium.
authors.forename: Jacoba J
authors.initials: JJ
authors.lastname: Louw
authors.forename: Anniek
authors.initials: A
authors.lastname: Corveleyn
authors.forename: Yaojuan
authors.initials: Y
authors.lastname: Jia
authors.forename: Greet
authors.initials: G
authors.lastname: Hens
authors.forename: Marc
authors.initials: M
authors.lastname: Gewillig
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
mesh_terms: D002675:Child, Preschool; D002872:Chromosome Deletion; D002972:Cleft Palate / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D006321:Heart / Q000254:growth & development* / Q000503:physiopathology; D006343:Heart Septal Defects / Q000235:genetics / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C491172:MEIS2 protein, human; D014157:Transcription Factors
keywords: cardiopathy; cleft lip; cleft palate; heart; intellectual disability; next generation sequencing (NGS)