CELSR3基因的双等位基因变异与中枢神经系统和泌尿系统异常有关。
Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies.
作者信息
Stegmann Jil D, Kalanithy Jeshurun C, Dworschak Gabriel C, Ishorst Nina, Mingardo Enrico, Lopes Filipa M, Ho Yee Mang, Grote Phillip, Lindenberg Tobias T, Yilmaz Öznur, Channab Khadija, Seltzsam Steve, Shril Shirlee, Hildebrandt Friedhelm, Boschann Felix, Heinen André, Jolly Angad, Myers Katherine, McBride Kim, Bekheirnia Mir Reza, Bekheirnia Nasim, Scala Marcello, Morleo Manuela, Nigro Vincenzo, Torella Annalaura, Pinelli Michele, Capra Valeria, Accogli Andrea, Maitz Silvia, Spano Alice, Olson Rory J, Klee Eric W, Lanpher Brendan C, Jang Se Song, Chae Jong-Hee, Steinbauer Philipp, Rieder Dietmar, Janecke Andreas R, Vodopiutz Julia, Vogel Ida, Blechingberg Jenny, Cohen Jennifer L, Riley Kacie, Klee Victoria, Walsh Laurence E, Begemann Matthias, Elbracht Miriam, Eggermann Thomas, Stoppe Arzu, Stuurman Kyra, van Slegtenhorst Marjon, Barakat Tahsin Stefan, Mulhern Maureen S, Sands Tristan T, Cytrynbaum Cheryl, Weksberg Rosanna, Isidori Federica, Pippucci Tommaso, Severi Giulia, Montanari Francesca, Kruer Michael C, Bakhtiari Somayeh, Darvish Hossein, Reutter Heiko, Hagelueken Gregor, Geyer Matthias, Woolf Adrian S, Posey Jennifer E, Lupski James R, Odermatt Benjamin, Hilger Alina C
机构信息
Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, 53127, Germany.
Institute of Anatomy and Cell Biology, Medical Faculty, University of Bonn, Bonn, 53115, Germany.
出版信息
NPJ Genom Med. 2024 Mar 1;9(1):18. doi: 10.1038/s41525-024-00398-9.
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.
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名受影响个体，他们的CELSR3存在双等位基因变异。受影响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尿路先天性异常（CAKUT）合并（3/12）以及仅CAKUT（2/12）。对三维蛋白质结构的计算模拟表明，所鉴定变异的位置与外显率和表型表达有关。CELSR3在人类胚胎尿路中的免疫定位以及在荧光斑马鱼报告系中对Celsr3的瞬时抑制和拯救实验进一步支持了CELSR3在中枢神经系统和尿路形成中的胚胎作用。
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