Compound Heterozygous Mutations Involving Splicing Mutations Cause Rothmund-Thomson Syndrome in Two Chinese Families  

作　　者：Chao-Lan Pan Qiao-Yu Cao Yue Li Jia Zhang Zhen Zhang Yu-Meng Wang Fu-Ying Chen Ru-Hong Cheng Xiao-Xiao Wang Zhi-Rong Yao Zhi-Yong Lu Ming Li 

机构地区：[1]Department of Dermatology,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China [2]Institute of Dermatology,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China.

出　　处：《International Journal of Dermatology and Venereology》2021年第2期76-81,共6页国际皮肤性病学杂志（英文）

基　　金：National Nature Science Foundation of China(Nos.82073422 and 81874239);Shanghai Health System Excellent Academic Leader Training Project(No.2018BR22);Pujiang Talents Program(No.18PJ1407300)。

摘　　要：Objective:Biallelic mutations in the RecQ like helicase(RECQL)4 gene,a guardian of the genome,cause Rothmund-Thomson syndrome type II(RTS-II).Two Chinese girls with mild-phenotype RTS-II mainly restricted to their skin are herein described.Methods:Blood specimens from two families with mild-phenotype RTS-II were collected.DNA isolation,RNA isolation and complementary DNA synthesis,and next-generation sequencing using a multi-gene panel were applied to verify the underlying pathogenic variants in the causativeRECQL4 gene.Results:We analyzed two patients with mild phenotypes.One patient had an unreported paternal c.2885+1G>A alteration in intervening sequence 16 and the previously reported maternal exon 14 c.2272C>T(p.R758X),both resulting in premature termination codons.The other patient carried two novel alterations,c.2886-1G>A and c.2752G>T(p.E918X).Complementary DNA sequencing showed that different splice-site mutations within the same intron could lead to completely different splicing modes.Conclusion:We identified three novel pathogenicRECQL4 variants in two patients with RTS,thus expanding the mutational spectrum of RTS-II.We also explored their pathogenic effect by transcripts analysis to address genotype-phenotype correlations.

关 键 词：exon-skipping GENODERMATOSIS RECQL4 variants Rothmund-Thomson syndrome splice-site mutation 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]