ArticleAmerican journal of human genetics2016
Bi-allelic Mutations in PKD1L1 Are Associated with Laterality Defects in Humans.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Genetics in Heterotaxy: A Case Series and Literature Review on DNAH9, PKD1L1, MMP21, and GDF1.Clinical genetics · 2026Pooled it
- The genetics of situs inversus without primary ciliary dyskinesia.Scientific reports · 2020Trial
- Structural and functional brain asymmetry in relation to heterogeneous causes of situs inversus totalis.Brain structure & function · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency.The Journal of clinical endocrinology and metabolism · 2025Article
- Genetic findings of children with congenital heart diseases using chromosomal microarray and trio-based whole exome sequencing.Scientific reports · 2025Article
- CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.American journal of human genetics · 2025Article
- Optical genome mapping uncovers clinically relevant structural variants in congenital heart disease with heterotaxy.Frontiers in genetics · 2025Article
- Breaking Left-Right Symmetry by the Interplay of Planar Cell Polarity, Calcium Signaling and Cilia.Cells · 2024Review
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
- Article
- Human Genetics of Defects of Situs.Advances in experimental medicine and biology · 2024Review
- Emerging principles of primary cilia dynamics in controlling tissue organization and function.The EMBO journal · 2023Review
- Loss of zebrafish pkd1l1 causes biliary defects that have implications for biliary atresia splenic malformation.Disease models & mechanisms · 2023Article
- Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants.American journal of medical genetics. Part A · 2023Article
- Are Genetic Modifiers the Answer to Different Responses to Hydroxyurea Treatment?-A Pharmacogenetic Study in Sickle Cell Anemia Angolan Children.International journal of molecular sciences · 2023Article
- Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy.Hepatology (Baltimore, Md.) · 2023Article
- Polycystin Channel Complexes.Annual review of physiology · 2023Review
- Multiple pkd and piezo gene family members are required for atrioventricular valve formation.Nature communications · 2023Article
- LOF variants identifying candidate genes of laterality defects patients with congenital heart disease.PLoS genetics · 2022Article
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 1 country.
Funding
Abstract
Disruption of the establishment of left-right (L-R) asymmetry leads to situs anomalies ranging from situs inversus totalis (SIT) to situs ambiguus (heterotaxy). The genetic causes of laterality defects in humans are highly heterogeneous. Via whole-exome sequencing (WES), we identified homozygous mutations in PKD1L1 from three affected individuals in two unrelated families. PKD1L1 encodes a polycystin-1-like protein and its loss of function is known to cause laterality defects in mouse and medaka fish models. Family 1 had one fetus and one deceased child with heterotaxy and complex congenital heart malformations. WES identified a homozygous splicing mutation, c.6473+2_6473+3delTG, which disrupts the invariant splice donor site in intron 42, in both affected individuals. In the second family, a homozygous c.5072G>C (p.Cys1691Ser) missense mutation was detected in an individual with SIT and congenital heart disease. The p.Cys1691Ser substitution affects a highly conserved cysteine residue and is predicted by molecular modeling to disrupt a disulfide bridge essential for the proper folding of the G protein-coupled receptor proteolytic site (GPS) motif. Damaging effects associated with substitutions of this conserved cysteine residue in the GPS motif have also been reported in other genes, namely GPR56, BAI3, and PKD1 in human and lat-1 in C. elegans, further supporting the likely pathogenicity of p.Cys1691Ser in PKD1L1. The identification of bi-allelic PKD1L1 mutations recapitulates previous findings regarding phenotypic consequences of loss of function of the orthologous genes in mice and medaka fish and further expands our understanding of genetic contributions to laterality defects in humans.
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