MEIS2 Involvement in Cardiac Development, Cleft Palate, and Intellectual Disability

作者：Louw Jacoba J; Corveleyn Anniek; Jia Yaojuan; Hens Greet; Gewillig Marc; Devriendt Koenraad^*

来源：American Journal of Medical Genetics, Part A, 2015, 167A(5): 1142-1146.

DOI：10.1002/ajmg.a.36989

• cleft palate
• cleft lip
• cardiopathy
• heart
• intellectual disability
• next generation sequencing (NGS)

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.

• 出版日期2015-5