Shimojima Keiko, Narai Satoshi, Togawa Masami, Doumoto Tomotsune, Sangu Noriko, Vanakker Olivier M, de Paepe Anne, Edwards Matthew, Whitehall John, Brescianini Sally, Petit Florence, Andrieux Joris, Yamamoto Toshiyuki
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
Department of Pediatrics, Tottori Prefectural Central Hospital, Tottori, Japan.
Eur J Med Genet. 2016 Oct;59(10):502-6. doi: 10.1016/j.ejmg.2016.09.008. Epub 2016 Sep 12.
There are no published reports of patients harboring microdeletions involving the 7p22.1 region. Although 7p22.1 microdeletions are rare, some reports have shown microduplications encompassing this region. In this study, we report five patients with overlapping deletions of the 7p22.1 region. The patients exhibited clinical similarities including non-specific developmental delay, short stature, microcephaly, and other distinctive features. The shortest region of overlap within the 7p22.1 region includes five genes, FBXL18, ACTB, FSCN1, RNF216, and ZNF815P. Of these genes, only ACTB is known to be associated with an autosomal dominant trait. Dominant negative mutations in ACTB are responsible for Baraitser-Winter syndrome 1. We analyzed ACTB expression in immortalized lymphocytes derived from one of the patients and found that it was reduced to approximately half that observed in controls. This indicates that ACTB expression is linearly correlated with the gene copy number. We suggest that haploinsufficiency of ACTB may be responsible for the clinical features of patients with 7p22.1 microdeletions.
目前尚无关于携带涉及7p22.1区域微缺失患者的公开报道。尽管7p22.1微缺失很罕见，但一些报道显示存在包含该区域的微重复。在本研究中，我们报告了5例7p22.1区域存在重叠缺失的患者。这些患者表现出临床相似性，包括非特异性发育迟缓、身材矮小、小头畸形以及其他独特特征。7p22.1区域内最短的重叠区域包含5个基因，即FBXL18、ACTB、FSCN1、RNF216和ZNF815P。在这些基因中，仅已知ACTB与常染色体显性性状相关。ACTB中的显性负性突变是导致巴赖特-温特综合征1的原因。我们分析了来自其中1例患者的永生化淋巴细胞中ACTB的表达，发现其表达水平降至对照组观察值的约一半。这表明ACTB表达与基因拷贝数呈线性相关。我们认为，ACTB单倍剂量不足可能是7p22.1微缺失患者临床特征的原因。
