Division of Medical Genetics, University Children's Hospital and Department of Biomedicine, Römergasse 8,Basel, Switzerland.
Clin Genet. 2011 Jan;79(1):79-85. doi: 10.1111/j.1399-0004.2010.01590.x. Epub 2010 Nov 22.
Submicroscopic chromosomal anomalies play an important role in the aetiology of intellectual disability (ID) and have been shown to account for up to 10% of non-syndromic forms. We present a family with two affected boys compatible with X-linked inheritance of a phenotype of severe neurodevelopmental disorder co-segregating with a deletion in Xp22.11 exclusively containing the PTCHD1 gene. Although the exact function of this gene is unknown to date, the structural overlap of its encoded patched domain-containing protein 1, the transmembrane protein involved in the sonic hedgehog pathway, and its expression in human cortex and cerebellum as well as in mice and drosophila brain suggests a causative role of its nullisomy in the developmental phenotype of our family. Our findings support the recent notions that PTCHD1 may play a role in X-linked intellectual disability (XLID) and autism disorders.
亚显微染色体异常在智力障碍（ID）的发病机制中起着重要作用，据报道，其占非综合征形式的比例高达 10%。我们介绍了一个家系，其中有两个受影响的男孩，其表型符合 X 连锁遗传，表现为严重的神经发育障碍，与 Xp22.11 缺失共分离，该缺失仅包含 PTCHD1 基因。尽管该基因的确切功能尚不清楚，但它编码的 patched 结构域包含蛋白 1 的结构重叠，该蛋白参与 sonic hedgehog 途径，其在人皮层和小脑以及小鼠和果蝇大脑中的表达表明其在我们家系的发育表型中具有缺失的因果作用。我们的发现支持了最近的观点，即 PTCHD1 可能在 X 连锁智力障碍（XLID）和自闭症障碍中发挥作用。
