Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Am J Med Genet A. 2013 Sep;161A(9):2158-66. doi: 10.1002/ajmg.a.36046. Epub 2013 Aug 2.
Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID). Microduplications of 5q35.2-q35.3 including NSD1 have been reported in only five patients so far and described clinically as a reversed Sos resulting from a hypothetical gene dosage effect of NSD1. Here, we report on nine patients from five families with interstitial duplication 5q35 including NSD1 detected by molecular karyotyping. The clinical features of all 14 individuals are reviewed. Patients with microduplications including NSD1 appear to have a consistent phenotype consisting of short stature, microcephaly, learning disability or mild to moderate ID, and distinctive facial features comprising periorbital fullness, short palpebral fissures, a long nose with broad or long nasal tip, a smooth philtrum and a thin upper lip vermilion. Behavioral problems, ocular and minor hand anomalies may be associated. Based on our findings, we discuss the possible etiology and conclude that it is possible, but so far unproven, that a gene dosage effect of NSD1 may be the major cause.
NSD1 基因失活突变和包含 NSD1 的 5q35 微缺失是 Sotos 综合征（Sos）的主要病因，其特征是过度生长、大头畸形、特征性面容和不同程度的智力障碍（ID）。迄今为止，仅在五名患者中报道了 5q35.2-q35.3 微重复，包括 NSD1，并被描述为由于 NSD1 的假设基因剂量效应而导致的反向 Sos。在这里，我们报告了五个家庭的九名患者，他们通过分子核型分析检测到 NSD1 存在 5q35 间质性重复。回顾了所有 14 个人的临床特征。包括 NSD1 的微重复患者似乎具有一致的表型，包括身材矮小、小头畸形、学习障碍或轻度至中度 ID，以及独特的面部特征，包括眶周饱满、短睑裂、长鼻子、宽或长鼻尖、光滑人中沟和薄上唇红唇。可能与行为问题、眼部和手部小畸形有关。基于我们的发现，我们讨论了可能的病因，并得出结论，虽然尚未证实，但 NSD1 的基因剂量效应可能是主要原因。
