De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux


MEIS2 aberrations are considered to be the cause of intellectual disability, cleft palate and cardiac septal defect, as MEIS2 copy number variation is often observed with these phenotypes. To our knowledge, only one nucleotide-level change—specifically, an in-frame MEIS2 deletion—has so far been reported. Here, we report a female patient with a de novo nonsense mutation (c.611C>G, p.Ser204*) in MEIS2. She showed severe intellectual disability, moderate motor/verbal developmental delay, cleft palate, cardiac septal defect, hypermetropia, severe feeding difficulties with gastro-esophageal reflux and constipation. By reviewing this patient and previous patients with MEIS2 point mutations, we found that feeding difficulty with gastro-esophageal reflux appears to be one of the core clinical features of MEIS2 haploinsufficiency, in addition to intellectual disability, cleft palate and cardiac septal defect.

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We would like to thank the patient and her family for participating in this study. We also thank Ms. S Sugimoto and K Takabe for their technical assistance. This work was supported in part by a grant for Research on Measures for Intractable Diseases; a grant for Comprehensive Research on Disability Health and Welfare, the Strategic Research Program for Brain Science (SRPBS), a grant for Initiative on Rare and Undiagnosed Diseases in Pediatrics from Japan Agency for Medical Research and Development (AMED); a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); Grants-in-Aid for Scientific Research (B and C) and Challenging Exploratory Research from the Japan Society for the Promotion of Science (JSPS); the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Japan Science and Technology Agency (JST); the Takeda Science Foundation; the Yokohama Foundation for Advancement of Medical Science; and the Hayashi Memorial Foundation for Female Natural Scientists.

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Correspondence to Noriko Miyake or Naomichi Matsumoto.

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