Authors
Jeremiah Martino, Qingxue Liu, Katarina Vukojevic, Juntao Ke, Tze Y Lim, Atlas Khan, Yask Gupta, Alejandra Perez, Zonghai Yan, Hila Milo Rasouly, Natalie Vena, Natalie Lippa, Jessica L Giordano, Marijan Saraga, Mirna Saraga-Babic, Rik Westland, Monica Bodria, Giorgio Piaggio, Pavan K Bendapudi, Alejandro D Iglesias, Ronald J Wapner, Velibor Tasic, Fan Wang, Iuliana Ionita-Laza, Gian Marco Ghiggeri, Krzysztof Kiryluk, Rosemary V Sampogna, Cathy L Mendelsohn, Vivette D D’Agati, Ali G Gharavi, Simone Sanna-Cherchi
Publication date
2023/12/1
Journal
Genetics in Medicine
Volume
25
Issue
12
Pages
100983
Publisher
Elsevier
Description
Purpose
Previous work identified rare variants in DSTYK associated with human congenital anomalies of the kidney and urinary tract (CAKUT). Here, we present a series of mouse and human studies to clarify the association, penetrance, and expressivity of DSTYK variants.
Methods
We phenotypically characterized Dstyk knockout mice of 3 separate inbred backgrounds and re-analyzed the original family segregating the DSTYK c.654+1G>A splice-site variant (referred to as “SSV” below). DSTYK loss of function (LOF) and SSVs were annotated in individuals with CAKUT, epilepsy, or amyotrophic lateral sclerosis vs controls. A phenome-wide association study analysis was also performed using United Kingdom Biobank (UKBB) data.
Results
Results demonstrate ∼20% to 25% penetrance of obstructive uropathy, at least, in C57BL/6J and FVB/NJ Dstyk–/– mice. Phenotypic penetrance increased to ∼40% in C3H/HeJ …
Scholar articles
J Martino, Q Liu, K Vukojevic, J Ke, TY Lim, A Khan… - Genetics in Medicine, 2023