Westphal Dominik Sebastian, Riedhammer Korbinian Maria, Kovacs-Nagy Reka, Meitinger Thomas, Hoefele Julia, Wagner Matias
Institute of Human Genetics, Technical University of Munich, Munich, Germany.
Institute of Human Genetics, Helmholtz Zentrum Munich, Neuherberg, Germany.
Neuropediatrics. 2018 Dec;49(6):401-404. doi: 10.1055/s-0038-1669926. Epub 2018 Sep 10.
Many genetic and nongenetic causes for developmental delay in childhood could be identified. Often, however, the molecular basis cannot be elucidated. As next-generation sequencing is becoming more frequently available in a diagnostic context, an increasing number of genetic variations are found as causative in children with developmental delay.We performed trio exome sequencing in a girl with developmental delay and minor dysmorphological features. Using a filter for de novo variants, the heterozygous missense variant c.812A>T, p.(Glu217Val) was found in the candidate gene in our patient. plays an important role in neuronal differentiation and hormonal regulation. To date, it has not been associated with monogenic disorders. Studies on knockout mice highlighted the importance of this protein in the development of the brain. Furthermore, microdeletions with an overlapping region including only and were linked to developmental delay in six unrelated families. Therefore, is a strong candidate gene for developmental delay, although functional assays proving this assumption still have to be done.
许多导致儿童发育迟缓的遗传和非遗传原因都可以被识别出来。然而，通常情况下，其分子基础却无法阐明。随着新一代测序技术在诊断领域越来越频繁地应用，越来越多的基因变异被发现是导致发育迟缓儿童发病的原因。我们对一名患有发育迟缓且有轻微畸形特征的女孩进行了三联体全外显子测序。通过对新生变异进行筛选，在我们的患者候选基因中发现了杂合错义变异c.812A>T，p.(Glu217Val)。 在神经元分化和激素调节中起重要作用。迄今为止，它尚未与单基因疾病相关联。对 基因敲除小鼠的研究突出了这种蛋白质在大脑发育中的重要性。此外，仅包含 和 的重叠区域的微缺失与六个无关家族的发育迟缓有关。因此， 是发育迟缓的一个强有力的候选基因，尽管仍需进行功能试验来证实这一假设。
