Johansson Stefan, Berland Siren, Gradek Gyri Aasland, Bongers Ernie, de Leeuw Nicole, Pfundt Rolph, Fannemel Madeleine, Rødningen Olaug, Brendehaug Atle, Haukanes Bjørn Ivar, Hovland Randi, Helland Gunnar, Houge Gunnar
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
Am J Med Genet A. 2014 Jul;164A(7):1622-6. doi: 10.1002/ajmg.a.36498. Epub 2014 Mar 26.
MEIS2 is a homeodomain-containing transcription factor of the TALE superfamily that has been proven important for development. We confirm and extend a recent single clinical report stating that deletions in MEIS2 can cause cleft palate [Crowley et al. (2010); Am J Med Genet 152A:1326-1327]. Here we report on five additional patients with 15q14 deletions of sizes 0.6, 0.6, 1.0, 1.9, and 4.8 Mb, respectively, all involving MEIS2. In addition, we present a family with four affected individuals and an intragenic 58 kb direct duplication disrupting MEIS2. In total, 7/9 cases had clefting, from mild (submucous cleft palate) to severe (cleft lip and palate), and 3/9 cases had ventricular septal defects. All cases had delayed motor development and most had learning disability, at worst in the mild intellectual disability range. The cases had overlapping facial features (broad forehead, finely arched eyebrows, mildly shortened philtrum, and tented upper lip) but individually they were not considered to be dysmorphic. Our results show that MEIS2 is a gene needed for palate closure. In syndromic cases of cleft palate, MEIS2 should be considered among the candidate genes, for example, in cases without 22q11.2 deletions.
MEIS2是TALE超家族中一个含同源结构域的转录因子，已被证明对发育很重要。我们证实并扩展了最近的一份单一临床报告，该报告指出MEIS2的缺失可导致腭裂[Crowley等人（2010年）；《美国医学遗传学杂志》152A:1326 - 1327]。在此，我们报告另外五例分别有大小为0.6、0.6、1.0、1.9和4.8兆碱基的15q14缺失的患者，所有这些缺失均涉及MEIS2。此外，我们展示了一个有四名受累个体的家族，其基因内有一个58千碱基的直接重复，破坏了MEIS2。总共9例中有7例有腭裂，从轻度（黏膜下腭裂）到重度（唇腭裂），9例中有3例有室间隔缺损。所有病例均有运动发育迟缓，大多数有学习障碍，最严重的处于轻度智力障碍范围。这些病例有重叠的面部特征（宽额头、细拱形眉毛、轻度缩短的人中、上唇呈帐篷状），但个体上不被认为是畸形的。我们的结果表明MEIS2是腭裂闭合所需的基因。在综合征性腭裂病例中，例如在没有22q11.2缺失的病例中，应将MEIS2视为候选基因之一。
