A human laterality disorder associated with a homozygous WDR16 deletion
Open accessAbstract
The laterality in the embryo is determined by left-right asymmetric gene expression driven by the flow of extraembryonic fluid, which is maintained by the rotary movement of monocilia on the nodal cells. Defects manifest by abnormal formation and arrangement of visceral organs. The genetic etiology of defects not associated with primary ciliary dyskinesia is largely unknown. In this study, we investigated the cause of situs anomalies, including heterotaxy syndrome and situs inversus totalis, in a consanguineous family. Whole-exome analysis revealed a homozygous deleterious deletion in the WDR16 gene, which segregated with the phenotype. WDR16 protein was previously proposed to play a role in cilia-related signal transduction processes; the rat Wdr16 protein was shown to be confined to cilia-possessing tissues and severe hydrocephalus was observed in the wdr16 gene knockdown zebrafish. The phenotype associated with the homozygous deletion in our patients suggests a role for WDR16 in human laterality patterning. Exome analysis is a valuable tool for molecular investigation even in cases of large deletions.
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In humans, CFAP45 and CFAP52 are both associated with a human laterality defect but not PCD.
“Interestingly, in humans, CFAP45 and CFAP52 are both associated with a human laterality defect but not PCD79,80.”
From The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision (2022) · cites this paper as [80]
The Patients section reports laterality defects in siblings with a WDR16 deletion and says nasal testing excluded PCD in one sibling. The paper does not name CFAP45 or CFAP52 or establish that either is WDR16, so our copy cannot support the claim about both named genes. (LLM, conf=0.82)
Experimental — accuracy not yet measuredHuman orthologs of two semi-sterile hits have been found mutated in related familial conditions: CFAP43 (orthologous to CG17687) is mutated in patients with MMAF, and CFAP52 (orthologous to CG10064) is mutated in laterality disorder.
“CFAP43 (orthologous to CG17687) is mutated in patients with multiple morphological abnormalities of the sperm flagella (MMAF), and CFAP52 (orthologous to CG10064) is mutated in laterality disorder, a condition caused by defects in ciliary beating during development [45,46].”
From Functional unknomics: Systematic screening of conserved genes of unknown function (2023) · cites this paper as [46]
The Results and Discussion report a homozygous WDR16 deletion in family members with laterality disorders, supporting the disease association attributed to this paper. Our copy does not identify WDR16 as CFAP52 or establish the stated orthology to CG10064, so those gene-identity details cannot be verified from this source. (LLM, conf=0.82)
Experimental — accuracy not yet measuredCG10064 is a WD40 repeat protein, and mutation of its human ortholog, CFAP52, results in abnormal left-right asymmetry patterning, a process known to depend on motile cilia.
“CG10064 is a WD40 repeat protein, and mutation of its human ortholog, CFAP52, results in abnormal left-right asymmetry patterning, a process known to depend on motile cilia [46,86].”
From Functional unknomics: Systematic screening of conserved genes of unknown function (2023) · cites this paper as [46]
The Discussion identifies WDR16 as a WD40 repeat protein, and the Abstract and Results report a homozygous WDR16 deletion associated with abnormal human left-right patterning. The Introduction says motile cilia play a key role in that patterning. Our copy does not identify WDR16 as CFAP52 or establish CG10064 as its ortholog, so it does not support those identifications. (LLM, conf=0.84)
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- Authors
- Ta-Shma, A., Perles, Z., Yaacov, B., Werner, M., Frumkin, A., Rein, A. J., & Elpeleg, O.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Venue
- European Journal of Human Genetics
- Published
- 2014-12-03
- Volume
- 23
- Issue
- 9
- Pages
- 1262-1265
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC4538206
- OpenAlex
- W1984041667
- Cited by
- 70
- References
- 14
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 8 · 2023: 16 · 2022: 4 · 2021: 3 · 2020: 10 · 2019: 10 · 2018: 2 · 2017: 2 · 2015: 1
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- homozygous deletion, left-right asymmetry, heterotaxy syndrome, situs inversus totalis, ciliary signaling, nodal cells, primary ciliary dyskinesia, consanguineous family, hydrocephalus
- MeSH terms
- Animals, Base Sequence, Carrier Proteins, Cilia, Consanguinity, Female, Homozygote, Humans, Hydrocephalus, Infant, Levocardia, Molecular Sequence Data, Phenotype, Sequence Deletion, Sequence Analysis, DNA, Rats, Heterotaxy Syndrome, Exome
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