open access publication

Article, 2024

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

NPJ GENOMIC MEDICINE, ISSN 2056-7944, 2056-7944, Volume 9, 1, 10.1038/s41525-024-00398-9

Contributors

Stegmann, Jil D. (Corresponding author) [1] Kalanithy, Jeshurun C. [1] Dworschak, Gabriel C. [1] Ishorst, Nina [1] Mingardo, Enrico [1] Lopes, Filipa M. [2] Ho, Yee Mang [2] Grote, Phillip [3] Lindenberg, Tobias T. [1] Yilmaz, Oeznur [1] Channab, Khadija [1] Seltzsam, Steve [4] [5] [6] Shril, Shirlee [4] [5] [6] Hildebrandt, Friedhelm [4] [5] [6] Boschann, Felix [7] [8] [9] Heinen, Andre [10] [11] Jolly, Angad [12] Myers, Katherine [13] [14] [15] Mcbride, Kim [13] [14] [15] Bekheirnia, Mir Reza [12] Bekheirnia, Nasim [12] Scala, Marcello [16] [17] Morleo, Manuela [18] [19] [20] Nigro, Vincenzo [18] [19] [20] Torella, Annalaura [18] [19] [20] Pinelli, Michele [19] [20] [21] Capra, Valeria [16] [17] Accogli, Andrea [22] Maitz, Silvia [23] Spano, Alice [24] Olson, Rory J. [25] Klee, Eric W. [25] Lanpher, Brendan C. [25] Jang, Se Song [26] Chae, Jong-Hee [26] [27] Steinbauer, Philipp [28] Rieder, Dietmar [29] Janecke, Andreas R. [29] Vodopiutz, Julia [28] Vogel, Ida [30] Blechingberg, Jenny [30] Cohen, Jennifer L. [31] Riley, Kacie [31] Klee, Victoria [32] [33] [34] Walsh, Laurence E. [32] [33] [34] Begemann, Matthias [35] Elbracht, Miriam [35] Eggermann, Thomas [35] Stoppe, Arzu [35] Stuurman, Kyra [36] [37] van Slegtenhorst, Marjon [36] [37] Barakat, Tahsin Stefan [36] [37] Mulhern, Maureen S. [38] Sands, Tristan T. [38] Cytrynbaum, Cheryl [39] [40] Weksberg, Rosanna [39] [40] Isidori, Federica [41] Pippucci, Tommaso [41] Severi, Giulia [41] Montanari, Francesca [41] Kruer, Michael C. [42] [43] [44] Bakhtiari, Somayeh [42] [43] [44] Darvish, Hossein [45] Reutter, Heiko [1] [46] Hagelueken, Gregor [1] Geyer, Matthias [1] Woolf, Adrian S. [2] [47] Posey, Jennifer E. [12] Lupski, James R. [12] Odermatt, Benjamin [1] Hilger, Alina C. (Corresponding author) [46]

Affiliations

  1. [1] Univ Bonn, Inst Anat & Cell Biol, Med Fac, D-53115 Bonn, Germany
    2. [NORA names: Germany; Europe, EU; OECD];
  2. [2] Royal Manchester Childrens Hosp, Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, England
    3. [NORA names: United Kingdom; Europe, Non-EU; OECD];
  3. [3] Inst Tumor Biol & Expt Therapy, Georg Speyer Haus, D-60596 Frankfurt, Germany
    4. [NORA names: Germany; Europe, EU; OECD];
  4. [4] Harvard Med Sch, Boston Childrens Hosp, Dept Pediat, Div Nephrol, Boston, MA USA
    5. [NORA names: United States; America, North; OECD];
  5. [5] Harvard Med Sch, Boston Childrens Hosp, Dept Pediat, Div Nephrol, Boston, MA USA
    6. [NORA names: United States; America, North; OECD];

Abstract

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.

Data Provider: Clarivate

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