Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia
Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia
复制标题
DOI：
10.1086/508902
复制
发表时间：
2006-11-01
影响因子：
9.8
通讯作者：
Hannula-Jouppi, Katariina
中科院分区：
文献类型：
--
作者：
Feuk, Lars;Kalervo, Aino;Hannula-Jouppi, Katariina
FOXP2基因突变会导致发育性言语失用症（DVD），但相关病例仅有少数被描述。我们对13名DVD - 5患者进行了特征分析，其中5名患者具有跨越FOXP2基因的父源半合子缺失，1名患者存在中断FOXP2的易位，其余7名患者为7号染色体母源单亲二体（UPD7），这些患者同时被诊断为西尔弗 - 罗素综合征（SRS）。在这些患有DVD的个体中，所有可获取父母DNA的12名患者均显示缺乏父源FOXP2拷贝。还描述了另外5名具有父源遗传的FOXP2缺失，但临床信息不完整或表型过于复杂而无法正确评估的个体。4名DVD患者也符合自闭症谱系障碍的标准。具有父源UPD7或部分母源UPD7或FOXP2下游起始缺失的个体不患有DVD。通过实时定量聚合酶链反应，我们发现母源遗传的FOXP2相对表达不足。我们的研究结果表明，父源FOXP2的缺失是患有母源UPD7的SRS患者发生DVD的原因。这些数据还指出FOXP2的亲本来源差异表达在人类语言发育中起作用。
Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few cases have been described. We characterize 13 patients with DVD-5 with hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome (SRS). Of these individuals with DVD, all 12 for whom parental DNA was available showed absence of a paternal copy of FOXP2. Five other individuals with deletions of paternally inherited FOXP2 but with incomplete clinical information or phenotypes too complex to properly assess are also described. Four of the patients with DVD also meet criteria for autism spectrum disorder. Individuals with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction, we show the maternally inherited FOXP2 to be comparatively underexpressed. Our results indicate that absence of paternal FOXP2 is the cause of DVD in patients with SRS with maternal UPD7. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.