The Phenotypic Spectrum of Duplication 5q35.2-q35.3 Encompassing NSD1: Is It Really a Reversed Sotos Syndrome?
The Phenotypic Spectrum of Duplication 5q35.2-q35.3 Encompassing NSD1: Is It Really a Reversed Sotos Syndrome?
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DOI：
10.1002/ajmg.a.36046
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发表时间：
2013-09-01
影响因子：
2
通讯作者：
Moog, Ute
中科院分区：
文献类型：
--
作者：
Dikow, Nicola;Maas, Bianca;Moog, Ute
NSD 1的功能缺失突变和包含NSD 1的5 q35微缺失是Sotos综合征（Sos）的主要原因，其特征在于过度生长、大头畸形、特征性面容和可变智力残疾（ID）。到目前为止，仅在5名患者中报告了包括NSD 1在内的5q35.2-q35.3微重复，临床上将其描述为由NSD 1的假设基因剂量效应引起的反向Sos。在这里，我们报告了来自5个家庭的9名患者与间质重复5 q35，包括NSD 1的分子核型检测。所有14个人的临床特征进行了审查。包括NSD 1在内的微复制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，包括眶周丰满、短睑裂、长鼻子和宽或长鼻尖、光滑的人中和薄上唇朱红。行为问题，眼睛和轻微的手异常可能相关。根据我们的研究结果，我们讨论了可能的病因，并得出结论，这是可能的，但迄今尚未证实，NSD 1的基因剂量效应可能是主要原因。(c)2013 Wiley Periodicals，Inc.
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. (c) 2013 Wiley Periodicals, Inc.