Abstract：
The key features of patients with a microduplication 5q35.2q35.3 (including the NSD1 gene) are short stature, microcephaly, mild developmental delay, behavioral problems, digital anomalies and congenital anomalies of internal organs. This core phenotype can be viewed as the reversed phenotype of Sotos syndrome, which is caused by a microdeletion in the same chromosomal region or a pathogenic variant in the NSD1 gene, and includes tall stature and macrocephaly, developmental delay, and epilepsy. Here, we report on a patient and his mother, both with a 5q35.2q35.3 duplication, adding a fifth family to the recently published overview of 39 patients of Quintero-Rivera et al. Our patient had several congenital anomalies, intrauterine growth restriction with a persisting short stature, while his mother was only mildly affected with decreased growth parameters. In addition, he had hemophagogocytic lymphohistiocytosis (HLH) triggered by Haemophilus influenzae and was recently diagnosed with Ewing sarcoma. Our cases carry the smallest duplication published (ca 332 kb, arr[hg19] 5q35.2q35.3(176493106-176824785)x3) further narrowing the distal side of the critical region of the 5q35.2q35.3 duplication. Besides broadening the clinical phenotypic spectrum, our report indicates that the 5q35.2q35.3 microduplication also shows a large intra-familial variability and expression.
摘要：
微重复5q35.2q35.3（包括NSD1基因）患者的关键特征是身材矮小，小头畸形,轻度发育迟缓,行为问题,数字异常和内脏器官的先天性异常。这种核心表型可以看作是Sotos综合征的逆转表型，这是由相同染色体区域的微缺失或NSD1基因的致病变异引起的，包括身材高大和大头畸形，发育迟缓,和癫痫。这里,我们报道了一个病人和他的母亲,两者都有5q35.2q35.3的重复，在最近发表的Quintero-Rivera等人39例患者的概述中增加了第五个家庭。我们的病人有几个先天性异常，持续身材矮小的宫内生长受限，而他的母亲只受到生长参数下降的轻度影响。此外,他患有由流感嗜血杆菌引发的噬血细胞淋巴组织细胞增生症（HLH），最近被诊断为尤文肉瘤。我们的案例是发布的最小重复(大约332kb，arr[hg19]5q35.2q35.3（176493106-176824785）x3）进一步缩小5q35.2q35.3重复的关键区域的远端。除了拓宽临床表型谱，我们的报告表明，5q35.2q35.3微重复也显示出很大的家族内变异性和表达。
