pgen.1009971.g001.tif (1.73 MB)

Clinical characterization of Type 2 Rothmund-Thomson Syndrome patients in this study.

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posted on 2021-12-29, 18:24 authored by Brittany E. Jewell, An Xu, Dandan Zhu, Mo-Fan Huang, Linchao Lu, Mo Liu, Erica L. Underwood, Jun Hyoung Park, Huihui Fan, Julian A. Gingold, Ruoji Zhou, Jian Tu, Zijun Huo, Ying Liu, Weidong Jin, Yi-Hung Chen, Yitian Xu, Shu-Hsia Chen, Nino Rainusso, Nathaniel K. Berg, Danielle A. Bazer, Christopher Vellano, Philip Jones, Holger K. Eltzschig, Zhongming Zhao, Benny Abraham Kaipparettu, Ruiying Zhao, Lisa L. Wang, Dung-Fang Lee

(A) Pedigrees of the two families with RTS Type 2 and RECQL4 pathogenic variants reported in this study. (B) Photos show the classic poikiloderma on the face, ears, and arms of individual RTS-A at age 2 years (left panels, top and bottom). Note the sparing of the trunk and abdomen as well as sparse scalp hair and absence of eyebrows and presence of gastrostomy feeding tube. Middle panels illustrate variability in the severity of poikiloderma on the lower extremities in RTS-A (upper) and RTS-B (lower). Note hypoplastic thumb and dystrophic nails in RTS-A. Both individuals developed osteosarcoma. The right top panel shows an x-ray of the skeletal defect (radiohumeral synostosis, age 2 years) in RTS-A, and the bottom panel shows an MRI image of osteosarcoma that developed in the right proximal radius of RTS-A at age 10 years. This T1 fat-saturated, coronal, post-contrast view demonstrates diffuse solid enhancement of the tumor with some central areas of non-enhancement. (C) Sanger sequencing verifies biallelic RECQL4 (c. 2719C>T/Q907X) pathogenic variant in RTS-A fibroblasts (upper panel) and RECQL4 (1568G>C;1573delT and VS11+32del24) in RTS-B fibroblasts (middle and lower panels). (D) Immunoblotting indicates the loss of RECQL4 protein in RTS-A fibroblasts and the truncated RECQL4 protein in RTS-B fibroblasts. *, non-specific band.