Ma Wanlu, Mao Jiangfeng, Wang Xi, Duan Lian, Song Yuwen, Lian Xiaolan, Zheng Junjie, Liu Zhaoxiang, Nie Min, Wu Xueyan
Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Endocrinology, The Second Hospital of Shandong University, Jinan, China.
Front Genet. 2020 Jun 24;11:596. doi: 10.3389/fgene.2020.00596. eCollection 2020.
A large deletion in Xp22.3 can result in contiguous gene syndromes, including X-linked ichthyosis (XLI) and Kallmann syndrome (KS), presenting with short stature, chondrodysplasia punctata, intellectual disability, and strabismus. XLI and KS are caused by the deletion of and , respectively.
Two KS patients with XLI were screened to identify possible pathogenic mutations using whole exome sequencing. The clinical characteristics, molecular genetics, treatment outcomes, and genotype-phenotype association for each patient were analyzed.
We identified a novel 3,923 kb deletion within the Xp22.31 region (chrX: 5810838-9733877) containing , , , , , , and in patient 1, who presented with KS, XLI, obesity, hyperlipidemia, and strabismus. We identified a novel 5,807 kb deletion within the Xp22.31-p22.33 regions (chrX: 2700083-8507807) containing , , and other 24 genes in patient 2, who presented with KS, XLI, obesity, and strabismus. No developmental delay, abnormal speech development, or autistic behavior were noticed in either patient.
We identified two novel microdeletions in the X chromosome leading to KS and XLI. These findings contribute to the understanding of the molecular mechanisms that drive contiguous gene syndromes. Our research confirmed that the Kallmann-Ichthyosis phenotype is caused by microdeletions at the chromosome level.
Xp22.3区域的大片段缺失可导致连续性基因综合征，包括X连锁鱼鳞病（XLI）和卡尔曼综合征（KS），表现为身材矮小、点状软骨发育不良、智力残疾和斜视。XLI和KS分别由 和 的缺失引起。
对两名患有XLI的KS患者进行全外显子组测序，以确定可能的致病突变。分析了每位患者的临床特征、分子遗传学、治疗结果以及基因型-表型关联。
在患者1的Xp22.31区域（chrX: 5810838 - 9733877）发现一个新的3923 kb缺失，包含 、 、 、 、 、 和 ，该患者表现为KS、XLI、肥胖、高脂血症和斜视。在患者2的Xp22.31 - p22.33区域（chrX: 2700083 - 8507807）发现一个新的5807 kb缺失，包含 、 和其他24个基因，该患者表现为KS、XLI、肥胖和斜视。两名患者均未出现发育迟缓、言语发育异常或自闭症行为。
我们在X染色体上发现了两个导致KS和XLI的新微缺失。这些发现有助于理解导致连续性基因综合征的分子机制。我们的研究证实，卡尔曼 - 鱼鳞病表型是由染色体水平的微缺失引起的。
