Rothmund-Thomson Syndrome: novel pathogenic mutations and frequencies of variants in the RECQL4 and USB1 (C16orf57) gene

Content Provider	Scilit
Author	Suter, Aude-Annick Itin, Peter Heinimann, Karl Ahmed, Munaza Ashraf, Tazeen Fryssira, Helen Kini, Usha Lapunzina, Pablo Miny, Peter Sommerlund, Mette Suri, Mohnish Vaeth, Signe Vasudevan, Pradeep Gallati, Sabina
Copyright Year	2016
Description	Journal: Molecular Genetics & Genomic Medicine Background Poikiloderma is defined as a chronic skin condition presenting with a combination of punctate atrophy, areas of depigmentation, hyperpigmentation and telangiectasia. In a variety of hereditary syndromes such as Rothmund–Thomson syndrome (RTS), Clericuzio-type poikiloderma with neutropenia (PN) and Dyskeratosis Congenita (DC), poikiloderma occurs as one of the main symptoms. Here, we report on genotype and phenotype data of a cohort of 44 index patients with RTS or related genodermatoses. Methods DNA samples from 43 patients were screened for variants in the 21 exons of the RECQL4 gene using PCR, SSCP-PAGE analysis and/or Sanger sequencing. Patients with only one or no detectable mutation in the RECQL4 gene were additionally tested for variants in the 8 exons of the USB1 (C16orf57) gene by Sanger sequencing. The effect of novel variants was evaluated by phylogenic studies, single-nucleotide polymorphism (SNP) databases and in silico analyses. Results We identified 23 different RECQL4 mutations including 10 novel and one homozygous novel USB1 (C16orf57) mutation in a patient with PN. Moreover, we describe 31 RECQL4 and 8 USB1 sequence variants, four of them being novel intronic RECQL4 sequence changes that may have some deleterious effects on splicing mechanisms and need further evaluation by transcript analyses. Conclusion The current study contributes to the improvement of genetic diagnostic strategies and interpretation in RTS and PN that is relevant in order to assess the patients' cancer risk, to avoid continuous and inconclusive clinical evaluations and to clarify the recurrence risk in the families. Additionally, it shows that the phenotype of more than 50% of the patients with suspected Rothmund–Thomson disease may be due to mutations in other genes raising the need for further extended genetic analyses.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867568/pdf
Ending Page	366
Page Count	8
Starting Page	359
e-ISSN	23249269
DOI	10.1002/mgg3.209
Journal	Molecular Genetics & Genomic Medicine
Issue Number	3
Volume Number	4
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2016-02-24
Access Restriction	Open
Subject Keyword	Journal: Molecular Genetics & Genomic Medicine Poikiloderma with Neutropenia Recql4 Gene Rothmund–thomson Syndrome Usb1 (c16orf57) Gene
Content Type	Text
Resource Type	Article