PKD1L1 Is Involved in Congenital Chylothorax

Besides visceral heterotaxia, 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 exhibiting in two consecutive fetuses with...

Full description

Saved in:
Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2024-01, Vol.13 (2), p.149
Main Authors: Whitchurch, Jonathan B, Schneider, Sophia, Hilger, Alina C, Köllges, Ricarda, Stegmann, Jil D, Waffenschmidt, Lea, Dyer, Laura, Thiele, Holger, Dhabhai, Bhanupriya, Dakal, Tikam Chand, Müller, Andreas, Norris, Dominic P, Reutter, Heiko M
Format: Article
Language:English
Subjects:
Amino acids
Animals
chylothorax
Chylothorax - genetics
congenital
Congenital diseases
Edema
Embryos
Female
Fetus
Fetuses
Genes
Genetic Diseases, X-Linked
Genomes
Genomics
Humans
Hydrops Fetalis
Immunofluorescence
Kidney diseases
Lethality
Localization
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mice, Knockout
Mutation
PKD1L1
Pleural effusion
Pregnancy
Proteins
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Besides visceral heterotaxia, 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 exhibiting in two consecutive fetuses with severe hydrops, implicating a direct role of in fetal hydrops formation. Here, we performed an exome survey and identified ultrarare compound heterozygous variants in 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 mutant mouse embryos revealed about 20% of embryos display general edema and pleural effusion at 14.5 dpc. Immunofluorescence staining at 14.5 dpc in embryos displayed both normal and massively altered lymphatic vessel morphologies. Together, our studies suggest the implication of in congenital lymphatic anomalies, including CCTs.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells13020149