Germline NUP98 Variants in Two Siblings with a Rothmund-Thomson-Like Spectrum: Protein Functional Changes Predicted by Molecular Modeling

This dataset contains the data (*.vcf files) for the paper “Colombo EA, Valiante M, Uggeri M, Orro A, Majore S, Grammatico P, Gentilini D, Finelli P, Gervasini C, D'Ursi P, Larizza L. Germline NUP98 Variants in Two Siblings with a Rothmund-Thomson-Like Spectrum: Protein Functional Changes Predicted by Molecular Modeling. Int J Mol Sci. 2023 Feb 16;24(4):4028. doi: 10.3390/ijms24044028. PMID: 36835439; PMCID: PMC9965077. In this study, the authors report the first observation of biallelic NUP98 germline variants in two siblings presenting sparse eyebrows/eyelashes, bilateral cataracts, hypogonadism, skeletal defects, premature aging signs, a picture reminiscent of both Rothmund–Thomson syndrome type 2 (RTS2,OMIM#268400) and RTS type 1 (RTS1, OMIM#618625). Patients (negative for RECQL4 mutations) were tested by whole exome sequencing (WES) in order to identify the causative gene(s). WES on the affected siblings, their parents, and a healthy brother disclosed in both patients two homozygous highly linked non-synonymous variants of the NUP98 gene, which was present in the heterozygous state in the healthy parents.

本数据集包含对应学术论文的*.vcf格式文件数据，该论文为Colombo EA、Valiante M、Uggeri M、Orro A、Majore S、Grammatico P、Gentilini D、Finelli P、Gervasini C、D'Ursi P、Larizza L. 发表于《国际分子科学杂志（*Int J Mol Sci*）》的《两例携带生殖系NUP98变异的同胞呈现类Rothmund-Thomson表型：基于分子建模的蛋白质功能改变预测》，刊载于2023年2月16日，第24卷第4期，文章编号4028，DOI: 10.3390/ijms24044028，PMID: 36835439，PMCID: PMC9965077。本研究首次报道两例同胞携带双等位基因生殖系NUP98变异，患者表现为眉毛与睫毛稀疏、双侧白内障、性腺功能减退、骨骼发育异常、早衰体征，其表型兼具Rothmund-Thomson综合征2型（RTS2, OMIM#268400）与Rothmund-Thomson综合征1型（RTS1, OMIM#618625）的特征。经RECQL4基因突变检测呈阴性的患者，通过全外显子测序（Whole Exome Sequencing, WES）筛选致病基因。对患病同胞、其父母及一名健康兄长开展全外显子测序后，在两名患者体内均检出NUP98基因的两个纯合且高度连锁的非同义变异，该变异在健康父母体内以杂合状态存在。