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
• 来源期刊: 国际皮肤性病学杂志（英文）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: Original Articles
• 页码范围: 76-81
• 页数: 6页
• 语种: 中文
• DOI: 10.1097/JD9.0000000000000160

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 causative RECQL4 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 pathogenic RECQL4 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.