Pathogenic PHIP Variants are Variably Associated With CAKUT
de Fallois J, Sieckmann T, Schönauer R, Petzold F, Münch J, Pauly M, Vasileiou G, Findeisen C, Kampmeier A, Kuechler A, Reis A, Decker E, Bergmann C, Platzer K, Tasic V, Kirschner KM, Shril S, Hildebrandt F, Chung WK, Halbritter J (2024)
Publication Type: Journal article
Publication year: 2024
Journal
DOI: 10.1016/j.ekir.2024.05.024
Abstract
Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) represent the most common cause of chronic kidney disease in children. Although only 20% of cases can be genetically explained, the majority remain without an identified underlying etiology. The neurodevelopmental disorder Chung-Jansen syndrome (CHUJANS) is caused by haploinsufficiency of Pleckstrin homology domain-interacting protein (PHIP) and was previously associated with genital malformations. Anecdotal coincidence of CHUJANS and CAKUT prompted us to investigate whether urorenal malformations are part of the phenotypic spectrum of CHUJANS. Methods: Analysis of existing CHUJANS and CAKUT cohorts, consulting matchmaking platforms, and systematic literature review to look for additional patients with both CHUJANS and CAKUT. Prenatal expression studies in murine and human renal tissues to investigate the role for PHIP in kidney development. Results: We identified 4 novel and 8 published cases, indicating variable expressivity with a urorenogenital trait frequency of 5% to 35%. The prenatal expression studies supported a role for PHIP in normal kidney and urinary tract development. Conclusion: Pathogenic PHIP gene variants should be considered as causative in patients with syndromal CAKUT. Conversely, patients with CHUJANS should be clinically evaluated for urorenogenital manifestations. Because neurodevelopmental disorders are often associated with kidney phenotypes, an interdisciplinary re-evaluation offers promise in identifying incompletely penetrant kidney associations and uncovering novel molecular mechanisms of disturbed nephrogenesis.
Authors with CRIS profile
Melissa Pauly
Institute of Human Genetics
Georgia Vasileiou
Institute of Human Genetics
André Wiesmann da Silva Reis
Lehrstuhl für Humangenetik
Involved external institutions
Universität Leipzig
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Medizinische Genetik Mainz
Germany (DE)
Saints Cyril and Methodius University of Skopje / Универзитет „Св. Кирил и Методиј“ во Скопје
Republic of North Macedonia (MK)
Veterans Affairs Healthcare System Boston and Harvard Medical School
United States (USA) (US)
Germany (DE)
Charité - Universitätsmedizin Berlin
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Medizinische Genetik Mainz
Germany (DE)
Saints Cyril and Methodius University of Skopje / Универзитет „Св. Кирил и Методиј“ во Скопје
Republic of North Macedonia (MK)
Veterans Affairs Healthcare System Boston and Harvard Medical School
United States (USA) (US)
How to cite
APA:
de Fallois, J., Sieckmann, T., Schönauer, R., Petzold, F., Münch, J., Pauly, M.,... Halbritter, J. (2024). Pathogenic PHIP Variants are Variably Associated With CAKUT. Kidney International Reports. https://doi.org/10.1016/j.ekir.2024.05.024
MLA:
de Fallois, Jonathan, et al. "Pathogenic PHIP Variants are Variably Associated With CAKUT." Kidney International Reports (2024).
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