Rothmund-Thomson综合征一家系基因突变检测

doi:10.3760/cma.j.issn.0412-4030.2019.09.004

Chinese Journal of Dermatology ›› 2019, Vol. 52 ›› Issue (9): 607-610.doi: 10.3760/cma.j.issn.0412-4030.2019.09.004

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Mutation analysis in a pedigree with Rothmund-Thomson syndrome

Wang Jianbo¹, Yang Limin², Wang Chen¹, Jia Ning³, Li Ming⁴, Li Jianguo¹, Zhang Shoumin¹, Li Zhenlu¹

¹Department of Dermatology, Henan Provincial People′s Hospital, Zhengzhou University People′s Hospital, Zhengzhou 450003, China; ²Department of Dermatology, Huaxian Hospital, The First Affiliated Hospital of Xinxiang Medical University, Anyang 456400, Henan, China; ³Laboratory of Molecular Biology and Biochemistry, Key Laboratory of Gene Research of Anhui Province, Anhui Medical University, Hefei 230000, China; ⁴Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200082, China

Received:2018-12-11 Revised:2019-03-03 Online:2019-09-15 Published:2019-08-30
Contact: Zhang Shoumin E-mail:henanpifu@sina.com
Supported by:
Henan Provincial Project of Science and Technology（182102310580）

Abstract

Abstract: 【Abstract】 Objective To detect gene mutations in a pedigree with Rothmund-Thomson syndrome（RTS）. Methods Clinical data were collected from two patients （an older sister and a younger brother） and their family members in a Chinese pedigree of Han nationality with RTS. Blood samples were obtained from the two patients, their unaffected older brother, their parents and 100 unrelated healthy controls. DNA was extracted, and all the exons in the encoding area of the RECQL4 gene were amplified by PCR. Gene mutations were detected by a skin-targeted next-generation sequencing panel, and verified by Sanger sequencing. Results Two heterozygous mutations were identified in the RECQL4 gene of the two patients, including a splice site mutation c.2886-1G>A and an insertion mutation c.1013_1014insC, which were inherited from the father and mother of the patients respectively. Meanwhile, neither of the two mutations was observed in 100 unrelated healthy controls or the older brother of the patients. Conclusion The splice site mutation c.2886-1G>A and the insertion mutation c.1013_1014insC in the RECQL4 gene may contribute to the clinical phenotype of the patients in this pedigree with RTS.

Key words: Rothmund-Thomson syndrome, RECQL4 gene, Skin targeted sequencing panel

Wang Jianbo, Yang Limin, Wang Chen, Jia Ning, Li Ming, Li Jianguo, Zhang Shoumin, Li Zhenlu. Mutation analysis in a pedigree with Rothmund-Thomson syndrome[J].Chinese Journal of Dermatology, 2019, 52(9): 607-610.

References ［17］

［1］	Wang LL, Plon SE. Rothmund⁃Thomson syndrome. GeneReviews®［DB/OL］. Seattle: University of Washington, 1993 ⁃ 2019. （2019⁃01⁃03）［2018⁃12⁃10］. https://www.ncbi.nlm.nih.gov/books/NBK1237.
［2］	Colombo EA, Locatelli A, Cubells Sánchez L, et al. Rothmund⁃Thomson syndrome: insights from new patients on the genetic variability underpinning clinical presentation and cancer outcome［J］. Int J Mol Sci, 2018,19（4）. pii: E1103. doi: 10.3390/ ijms19041103.
［3］	Sangrithi MN, Bernal JA, Madine M, et al. Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund⁃Thomson syndrome［J］. Cell, 2005,121（6）:887⁃898. doi: 10.1016/ j.cell.2005.05.015.
［4］	Lu H, Shamanna RA, Keijzers G, et al. RECQL4 promotes DNA end resection in repair of DNA double⁃strand breaks［J］. Cell Rep, 2016,16（1）:161⁃173. doi: 10.1016/j.celrep.2016.05.079.
［5］	Fan W, Luo J. RecQ4 facilitates UV light⁃induced DNA damage repair through interaction with nucleotide excision repair factor xeroderma pigmentosum group A （XPA）［J］. J Biol Chem, 2008,283（43）:29037⁃29044. doi: 10.1074/jbc.M801928200.
［6］	Schurman SH, Hedayati M, Wang Z, et al. Direct and indirect roles of RECQL4 in modulating base excision repair capacity［J］. Hum Mol Genet, 2009,18（18）:3470⁃3483. doi: 10.1093/hmg/ddp291.
［7］	Ghosh AK, Rossi ML, Singh DK, et al. RECQL4, the protein mutated in Rothmund⁃Thomson syndrome, functions in telomere maintenance［J］. J Biol Chem, 2012,287（1）:196⁃209. doi: 10. 1074/jbc.M111.295063.
［8］	De S, Kumari J, Mudgal R, et al. RECQL4 is essential for the transport of p53 to mitochondria in normal human cells in the absence of exogenous stress［J］. J Cell Sci, 2012,125（Pt 10）:2509⁃2522. doi: 10.1242/jcs.101501.
［9］	Gupta S, De S, Srivastava V, et al. RECQL4 and p53 potentiate the activity of polymerase γ and maintain the integrity of the human mitochondrial genome［J］. Carcinogenesis, 2014,35（1）:34⁃45. doi: 10.1093/carcin/bgt315.
［10］	Larizza L, Roversi G, Volpi L. Rothmund⁃Thomson syndrome［J］. Orphanet J Rare Dis, 2010,5:2. doi: 10.1186/1750⁃1172⁃5⁃2.
［11］	Piard J, Aral B, Vabres P, et al. Search for ReCQL4 mutations in 39 patients genotyped for suspected Rothmund⁃Thomson/Baller⁃Gerold syndromes［J］. Clin Genet, 2015,87（3）:244⁃251. doi: 10. 1111/cge.12361.
［12］	Zhang J, Yan M, Cheng R, et al. A rare RECQL4 indel mutation in a Chinese patient with Rothmund⁃Thomson syndrome［J］. J Eur Acad Dermatol Venereol, 2016,30（11）:e159⁃e161. doi: 10. 1111/jdv.13466.
［13］	Bhoyrul B, Lindsay H, Robinson R, et al. Pili annulati in a case of Rothmund⁃Thomson syndrome with a novel frameshift mutation in RECQL4［J］. J Eur Acad Dermatol Venereol, 2018,32（6）:e221⁃e223. doi: 10.1111/jdv.14742.
［14］	Gui B, Song Y, Hu X, et al. Novel pathogenic RECQL4 variants in Chinese patients with Rothmund⁃Thomson syndrome［J］. Gene, 2018,654:110⁃115. doi: 10.1016/j.gene.2018.02.047.
［15］	Wang T, Chen L, She Q, et al. Four novel RECQL4 mutations in four Chinese patients with Rothmund⁃Thomson syndrome and analysis of RECQL4 mRNA expression level in one typical patient［J］. J Dermatol Sci, 2018,91（3）:335⁃337. doi: 10.1016/j.jdermsci.2018.06.005.
［16］	党林, 栗玉珍, 于淞. Rothmund⁃Thomson综合征一例RECQL4基因的突变分析［J］. 中华皮肤科杂志, 2009,42（1）:28⁃30. doi: 10.3760/cma.j.issn.0412⁃4030.2009.01.011.
［17］	王建波, 雷东春, 王伟霞, 等. 一对先天性大疱性鱼鳞病样红皮病双胞胎患者表型与角蛋白1基因突变研究［J］. 中华皮肤科杂志, 2018,51（3）:186⁃188. doi: 10.3760/cma.j.issn.0412⁃4030.2018.03.005.

Mutation analysis in a pedigree with Rothmund-Thomson syndrome

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