Polycystin-1-like protein 1
ciliary membrane
<i>PKD1L1</i> Is Involved in Congenital Chylothorax.
Besides visceral heterotaxia, <i>Pkd1l1</i> 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 <i>PKD1L1</i> exhibiting in two consecutive fetuses with severe hydrops, implicating a direct role of <i>PKD1L1</i> in fetal hydrops formation. Here, we performed an exome survey and identified ultrarare compound heterozygous variants in <i>PKD1L1</i> 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 <i>Pkd1l1</i> mutant mouse embryos revealed about 20% of <i>Pkd1l1<sup>-/-</sup></i> embryos display general edema and pleural effusion at 14.5 dpc. Immunofluorescence staining at 14.5 dpc in <i>Pkd1l1<sup>-/-</sup></i> embryos displayed both normal and massively altered lymphatic vessel morphologies. Together, our studies suggest the implication of <i>PKD1L1</i> in congenital lymphatic anomalies, including CCTs.