Compound Heterozygous Mutations Involving Splicing Mutations Cause Rothmund–Thomson Syndrome in Two Chinese Families
| Autor: | Qiao-Yu Cao, Zhen Zhang, Chaolan Pan, Yumeng Wang, Ruhong Cheng, Yue Li, Ming Li, Fu-Ying Chen, Xiao-Xiao Wang, Zhiyong Lu, Jia Zhang, Zhirong Yao |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | International Journal of Dermatology and Venerology, Vol 4, Iss 2, Pp 76-81 (2021) |
| ISSN: | 2641-8746 2096-5540 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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