This summary discusses chromosome 15q14 deletions and the loss of the MEIS2 gene. 15q14 deletions (deletions occurring within this region of the long arm of chromosome 15) are known to cause cleft palate, intellectual disability, congenital heart defects, and facial dysmorphism. Loss of the MEIS2 gene located within 15q14 has been attributed to these symptoms. To demonstrate the role of the MEIS2 gene the article reviews 23 patients with either a mutation in MEIS2 alone, or a 15q14 deletion that includes MEIS2. Comparison of these two groups of patients will determine which symptoms are caused by loss of MEIS2, and which may be caused by different genes located within 15q14.
Of the 23 patients studied, 9 had a mutation within MEIS2 alone, and 14 had a 15q14 deletion that encompassed multiple genes including MEIS2 . Both groups of patients shared very similar phenotypes, including palatal defects, heart defects, and intellectual disability. It shows that the MEIS2 gene is the main cause of this syndrome. Whether loss of other genes within this region may be contributing to the severity of these heart defects is unknown. For example, ACTC1 – also found within 15q14 – is a known cause of septal heart defects.
The magnitude of developmental issues was variable in the 23 patients, and ranged from slight learning problems to severe intellectual disability. Symptom severity was worse in patients with deletions of 15q14 than in patients with MEIS2 mutations alone, likely due to the loss of additional genes within this region. One feature that was present in 15q14 deletion patients and not in MEIS2 mutation patients was microcephaly. From these results, it is presumed that other genes within the 15q14 region may be contributing to proper brain development. However, potential genes within this region could not be identified in this study.
These observations further support the assumption that the loss of MEIS2 causes symptoms including palatal defects, heart defects, and intellectual disability. In 15q14 deletion patients, loss of this gene likely contributes to these symptoms. However, it should also be mentioned that additional genes within this region may also be contributing to symptom severity.
Verheije, et al. “Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability”. European Journal of Human Genetics 2019, v. 27 (2), 278-290.
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