Gui Baoheng, Song Yanning, Hu Xuyun, Li Hongdou, Qin Zailong, Su Jiasun, Li Chuan, Fan Xin, Li Mengting, Luo Jingsi, Feng Ying, Song Liping, Chen Shaoke, Gong Chunxiu, Shen Yiping
Department of Genetics and Metabolism, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530002, PR China; Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530002, PR China.
National Center for Children's Health, China, Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, The Capital Medical University, Beijing 100045, PR China.
Gene. 2018 May 15;654:110-115. doi: 10.1016/j.gene.2018.02.047. Epub 2018 Feb 17.
Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder mainly characterized by cutaneous poikiloderma, sparse hair, short stature and skeletal defects. Deleterious mutations in the RecQ-like DNA helicase type 4 (RECQL4) gene have been detected in approximately two-thirds of RTS cases.
Three Chinese patients from two unrelated families were enrolled for clinical evaluation. Targeted next-generation sequencing (NGS) using a custom panel consisting of 705 short-stature-related genes was performed for the probands. Variants detected by NGS were confirmed by Sanger sequencing and examined in family members.
The probands presented with characteristic features of severe growth delay, poikiloderma mostly on the face, buttocks and extremities, sparse or absent hair, eyelashes, and eyebrows, forearm reduction defects, small hands with hypoplasia of the middle phalanx (little finger) in one of the probands, epicanthus, hypertelorism, and dental abnormalities. In addition, novel auricle features and other rare facial features, including narrow palpebral fissure, depressed nasal bridge, and small chin were exhibited. Four novel RECQL4 variants were identified, including three pathogenic frameshift variants, c.1724_1725delAC, p.His575fs7; c.2421dupT, p.Asp808; c.1770_1807del, p.Pro591fs*2, and one likely pathogenic missense variant, c.691G>A, p.Gly231Ser.
Our study expands the mutational spectrum of RECQL4 gene and reveals novel phenotypes observed in Chinese RTS patients.
罗思蒙德 - 汤姆森综合征（RTS）是一种罕见的常染色体隐性疾病，主要特征为皮肤异色症、毛发稀疏、身材矮小和骨骼缺陷。在大约三分之二的RTS病例中检测到了类RecQ DNA解旋酶4（RECQL4）基因的有害突变。
招募了来自两个无关家庭的三名中国患者进行临床评估。对先证者进行了靶向二代测序（NGS），使用包含705个与身材矮小相关基因的定制基因panel。通过NGS检测到的变异通过桑格测序进行确认，并在家庭成员中进行检测。
先证者表现出严重生长发育迟缓的特征性表现，皮肤异色症主要出现在面部、臀部和四肢，毛发、睫毛和眉毛稀疏或缺失，前臂发育不全缺陷，一名先证者双手小，中指（小指）发育不全，内眦赘皮，眼距增宽和牙齿异常。此外，还表现出新颖的耳廓特征和其他罕见的面部特征，包括睑裂狭窄、鼻梁凹陷和小下巴。鉴定出四个新的RECQL4变异，包括三个致病性移码变异，c.1724_1725delAC，p.His575fs7；c.2421dupT，p.Asp808；c.1770_1807del，p.Pro591fs*2，以及一个可能致病的错义变异，c.691G>A，p.Gly231Ser。
我们的研究扩展了RECQL4基因的突变谱，并揭示了中国RTS患者中观察到的新表型。
