A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family
Abstract Background Dyskeratosis congenita (DC) is an inherited telomeropathy characterized by mucocutaneous dysplasia, bone marrow failure, cancer predisposition, and other somatic abnormalities. Cells from patients with DC exhibit short telomere. The genetic basis of the majority of DC cases remai...
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| Format: | Article |
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BMC
2018-03-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-018-0549-1 |
| _version_ | 1818946577202413568 |
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| author | Yingqi Shao Sizhou Feng Jinbo Huang Jiali Huo Yahong You Yizhou Zheng |
| author_facet | Yingqi Shao Sizhou Feng Jinbo Huang Jiali Huo Yahong You Yizhou Zheng |
| author_sort | Yingqi Shao |
| collection | DOAJ |
| description | Abstract Background Dyskeratosis congenita (DC) is an inherited telomeropathy characterized by mucocutaneous dysplasia, bone marrow failure, cancer predisposition, and other somatic abnormalities. Cells from patients with DC exhibit short telomere. The genetic basis of the majority of DC cases remains unknown. Methods A 2 generational Chinese Han family with DC was studied using targeted capture and next-generation sequencing to identify the underlying DC-related mutations. Results In this study, we identified a unique homozygous WD repeat containing antisense to TP53 (WRAP53) Arg298Trp mutation in the proband with DC and heterozygous WRAP53 Arg298Trp mutations in his asymptomatic, consanguineous parents and his sister, indicating an autosomal recessive inheritance mode. The proband with the homozygous WRAP53 Arg298Trp mutation had short telomere, classic clinical symptoms, and no response to danazol, glucocorticoid or cyclosporin A. Conclusions Thus, we reported for the first time that a unique homozygous WRAP53 mutation site underlies the development of DC. |
| first_indexed | 2024-12-20T08:17:13Z |
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| id | doaj.art-beb1cfd602fc4c4094ced0b25a2c4a5d |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-20T08:17:13Z |
| publishDate | 2018-03-01 |
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| spelling | doaj.art-beb1cfd602fc4c4094ced0b25a2c4a5d2022-12-21T19:47:05ZengBMCBMC Medical Genetics1471-23502018-03-011911710.1186/s12881-018-0549-1A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han familyYingqi Shao0Sizhou Feng1Jinbo Huang2Jiali Huo3Yahong You4Yizhou Zheng5State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical CollegeAbstract Background Dyskeratosis congenita (DC) is an inherited telomeropathy characterized by mucocutaneous dysplasia, bone marrow failure, cancer predisposition, and other somatic abnormalities. Cells from patients with DC exhibit short telomere. The genetic basis of the majority of DC cases remains unknown. Methods A 2 generational Chinese Han family with DC was studied using targeted capture and next-generation sequencing to identify the underlying DC-related mutations. Results In this study, we identified a unique homozygous WD repeat containing antisense to TP53 (WRAP53) Arg298Trp mutation in the proband with DC and heterozygous WRAP53 Arg298Trp mutations in his asymptomatic, consanguineous parents and his sister, indicating an autosomal recessive inheritance mode. The proband with the homozygous WRAP53 Arg298Trp mutation had short telomere, classic clinical symptoms, and no response to danazol, glucocorticoid or cyclosporin A. Conclusions Thus, we reported for the first time that a unique homozygous WRAP53 mutation site underlies the development of DC.http://link.springer.com/article/10.1186/s12881-018-0549-1WRAP53Dyskeratosis congenitaHomozygous |
| spellingShingle | Yingqi Shao Sizhou Feng Jinbo Huang Jiali Huo Yahong You Yizhou Zheng A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family BMC Medical Genetics WRAP53 Dyskeratosis congenita Homozygous |
| title | A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family |
| title_full | A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family |
| title_fullStr | A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family |
| title_full_unstemmed | A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family |
| title_short | A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family |
| title_sort | unique homozygous wrap53 arg298trp mutation underlies dyskeratosis congenita in a chinese han family |
| topic | WRAP53 Dyskeratosis congenita Homozygous |
| url | http://link.springer.com/article/10.1186/s12881-018-0549-1 |
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