CELSR3 的双等位基因变异与中枢神经系统和泌尿系统异常有关。

IF 4.7 2区医学 Q1 GENETICS & HEREDITY NPJ Genomic Medicine Pub Date : 2024-03-01 DOI:10.1038/s41525-024-00398-9

Jil D Stegmann, Jeshurun C Kalanithy, Gabriel C Dworschak, Nina Ishorst, Enrico Mingardo, Filipa M Lopes, Yee Mang Ho, Phillip Grote, Tobias T Lindenberg, Öznur Yilmaz, Khadija Channab, Steve Seltzsam, Shirlee Shril, Friedhelm Hildebrandt, Felix Boschann, André Heinen, Angad Jolly, Katherine Myers, Kim McBride, Mir Reza Bekheirnia, Nasim Bekheirnia, Marcello Scala, Manuela Morleo, Vincenzo Nigro, Annalaura Torella, Michele Pinelli, Valeria Capra, Andrea Accogli, Silvia Maitz, Alice Spano, Rory J Olson, Eric W Klee, Brendan C Lanpher, Se Song Jang, Jong-Hee Chae, Philipp Steinbauer, Dietmar Rieder, Andreas R Janecke, Julia Vodopiutz, Ida Vogel, Jenny Blechingberg, Jennifer L Cohen, Kacie Riley, Victoria Klee, Laurence E Walsh, Matthias Begemann, Miriam Elbracht, Thomas Eggermann, Arzu Stoppe, Kyra Stuurman, Marjon van Slegtenhorst, Tahsin Stefan Barakat, Maureen S Mulhern, Tristan T Sands, Cheryl Cytrynbaum, Rosanna Weksberg, Federica Isidori, Tommaso Pippucci, Giulia Severi, Francesca Montanari, Michael C Kruer, Somayeh Bakhtiari, Hossein Darvish, Heiko Reutter, Gregor Hagelueken, Matthias Geyer, Adrian S Woolf, Jennifer E Posey, James R Lupski, Benjamin Odermatt, Alina C Hilger

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引用次数: 0

摘要

CELSR3编码一种平面细胞极性蛋白。我们描述了来自 11 个独立家庭的 12 名患有 CELSR3 双等位基因变异的患者。受影响的个体表现出重叠的表型谱，包括中枢神经系统（CNS）异常（7/12）、中枢神经系统异常与肾脏和泌尿道先天性异常（CAKUT）合并（3/12）以及仅CAKUT（2/12）。三维蛋白质结构的计算模拟表明，已确定的变异体的位置与穿透性和表型表达有关。CELSR3 在人类胚胎泌尿道中的免疫定位以及 Celsr3 在荧光斑马鱼报告基因系中的瞬时抑制和拯救实验进一步支持了 CELSR3 在中枢神经系统和泌尿道形成中的胚胎作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.

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来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.