Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.
Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.
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DOI：
10.1002/humu.21362
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发表时间：
2010-11
期刊：
影响因子：
3.9
通讯作者：
Strom, Tim M.
中科院分区：
文献类型：
--
作者：
Horn, Denise;Kapeller, Johannes;Rivera-Brugues, Nria;Moog, Ute;Lorenz-Depiereux, Bettina;Eck, Sebastian;Hempel, Maja;Wagenstaller, Janine;Gawthrope, Alex;Monaco, Anthony P.;Bonin, Michael;Riess, Olaf;Wohlleber, Eva;Illig, Thomas;Bezzina, Connie R.;Franke, Andre;Spranger, Stephanie;Villavicencio-Lorini, Pablo;Seifert, Wenke;Rosenfeld, Jochen;Klopocki, Eva;Rappold, Gudrun A.;Strom, Tim M.
精神发育迟滞影响2-3%的人口，并显示出高遗传性。包括语言和言语技能明显受损的神经发育障碍发生频率较低。在大多数情况下，由于潜在遗传因素的异质性，智力低下伴或不伴言语和语言障碍的分子基础尚不清楚。我们对1523例智力低下患者进行了分子核型分析，以检测拷贝数变异（CNVs），包括缺失或重复。这些研究揭示了三个杂合重叠缺失只影响叉头盒P1（FOXP 1）基因。所有三名患者均患有中度智力迟钝和明显的语言和言语障碍。由于我们的结果与这些缺失的从头发生一致，我们认为它们是因果关系，尽管我们在4104个祖先匹配的对照中检测到了包括FOXP 1和其他基因在内的单个大缺失。这些发现对于FOXP 1和FOXP 2之间的结构和功能关系很有意义。FOXP 2的突变以前与发育性言语运动障碍的单基因病例有关。FOXP 1和FOXP 2都在鸣禽和人类大脑区域表达，这些区域对最终形成言语和语言的发育过程非常重要。©2010 Wiley-Liss公司。
Mental retardation affects 2-3% of the population and shows a high heritability. Neurodevelopmental disorders that include pronounced impairment in language and speech skills occur less frequently. For most cases, the molecular basis of mental retardation with or without speech and language disorder is unknown due to the heterogeneity of underlying genetic factors. We have used molecular karyotyping on 1523 patients with mental retardation to detect copy number variations (CNVs) including deletions or duplications. These studies revealed three heterozygous overlapping deletions solely affecting the forkhead box P1 (FOXP1) gene. All three patients had moderate mental retardation and significant language and speech deficits. Since our results are consistent with a de novo occurrence of these deletions, we considered them as causal although we detected a single large deletion including FOXP1 and additional genes in 4104 ancestrally matched controls. These findings are of interest with regard to the structural and functional relationship between FOXP1 and FOXP2. Mutations in FOXP2 have been previously related to monogenic cases of developmental verbal dyspraxia. Both FOXP1 and FOXP2 are expressed in songbird and human brain regions that are important for the developmental processes that culminate in speech and language. ©2010 Wiley-Liss, Inc.
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