Wu Qiuping, Weng Weiqi, Yuan Jinna, Xu Xiaoqin, Huang Ke, Dong Guanping, Fu Junfen, Wu Wei
Department of Endocrinology, The Affiliated Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, Zhejiang 310052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Jan 10;39(1):31-34. doi: 10.3760/cma.j.cn511374-20201020-00736.
To explore the genetic basis for a child with Rothmund-Thomson syndrome (RTS).
The child has featured poikeloderma, short stature, cataract, sparse hair and skeletal malformation. Peripheral blood samples of the child and her family members were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.
The child was found to harbor compound heterozygous variants of the RECQL4 gene, namely c.1048_1049delAG and c.2886-1G>A, among which c.2886-1G>A was unreported previously. According to the ACMG guidelines, the c.1048_1049delAG was predicted to be pathogenic (PVS1+PM3_Strong+PM2), while the c.2886-1G>A was predicted to be likely pathogenic (PVS1+PM2).
The compound heterozygous variants of the RECQL4 gene probably underlay the pathogenesis of RTS in this patient. Above finding has enriched the mutational spectrum of the RECQL4 gene.
探究一名患有罗思蒙德 - 汤姆森综合征（RTS）儿童的遗传基础。
该患儿具有皮肤异色症、身材矮小、白内障、头发稀疏和骨骼畸形等特征。采集了患儿及其家庭成员的外周血样本，并进行全外显子组测序。候选变异通过桑格测序进行验证。
发现该患儿携带RECQL4基因的复合杂合变异，即c.1048_1049delAG和c.2886-1G>A，其中c.2886-1G>A此前未见报道。根据美国医学遗传学与基因组学学会（ACMG）指南，c.1048_1049delAG被预测为致病（PVS1+PM3_Strong+PM2），而c.2886-1G>A被预测为可能致病（PVS1+PM2）。
RECQL4基因的复合杂合变异可能是该患者RTS发病机制的基础。上述发现丰富了RECQL4基因的突变谱。
