PKD1L1 Is Involved in Congenital Chylothorax

Whitchurch JB, Schneider S, Hilger AC, Köllges R, Stegmann JD, Waffenschmidt L, Dyer L, Thiele H, Dhabhai B, Dakal TC, Müller A, Norris DP, Reutter HM (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cells MDPI

Book Volume: 13

Journal Issue: 2

DOI: 10.3390/cells13020149

Abstract

Besides visceral heterotaxia, Pkd1l1 null mouse embryos exhibit general edema and perinatal lethality. In humans, congenital chylothorax (CCT) is a frequent cause of fetal hydrops. In 2021, Correa and colleagues reported ultrarare compound heterozygous variants in PKD1L1 exhibiting in two consecutive fetuses with severe hydrops, implicating a direct role of PKD1L1 in fetal hydrops formation. Here, we performed an exome survey and identified ultrarare compound heterozygous variants in PKD1L1 in two of the five case-parent trios with CCT. In one family, the affected carried the ultrarare missense variants c.1543G>A(p.Gly515Arg) and c.3845T>A(p.Val1282Glu). In the other family, the affected carried the ultrarare loss-of-function variant (LoF) c.863delA(p.Asn288Thrfs*3) and the ultrarare missense variant c.6549G>T(p.Gln2183His). Investigation of the variants' impact on PKD1L1 protein localization suggests the missense variants cause protein dysfunction and the LoF variant causes protein mislocalization. Further analysis of Pkd1l1 mutant mouse embryos revealed about 20% of Pkd1l1-/- embryos display general edema and pleural effusion at 14.5 dpc. Immunofluorescence staining at 14.5 dpc in Pkd1l1-/- embryos displayed both normal and massively altered lymphatic vessel morphologies. Together, our studies suggest the implication of PKD1L1 in congenital lymphatic anomalies, including CCTs.

Involved external institutions

Universitätsklinikum Bonn DE Germany (DE) MRC Harwell Institute GB United Kingdom (GB) Universität zu Köln DE Germany (DE) Mohanlal Sukhadia University / University of Udaipur IN India (IN)

How to cite

APA:

Whitchurch, J.B., Schneider, S., Hilger, A.C., Köllges, R., Stegmann, J.D., Waffenschmidt, L.,... Reutter, H.M. (2024). PKD1L1 Is Involved in Congenital Chylothorax. Cells, 13(2). https://dx.doi.org/10.3390/cells13020149

MLA:

Whitchurch, Jonathan B., et al. "PKD1L1 Is Involved in Congenital Chylothorax." Cells 13.2 (2024).

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