title: ANKS3 is mutated in a family with autosomal recessive laterality defect.
abstract: Laterality defects are heterogeneous groups of congenital malformations that arise from perturbed asymmetrical development of visceral organs. The central role of the motile cilia-generated nodal flow in breaking early embryonic symmetry is reflected in the large contribution of ciliary genes to the etiology of these disorders. In a consanguineous multiplex family with a laterality defect that resembles situs inversus totalis, and complex congenital heart disease, we combined autozygome and exome analysis to identify a novel homozygous variant in ANKS3. ANKS3 encodes a recently described ciliary protein with known interaction with other ciliary proteins, and deficiency of its zebrafish ortholog causes laterality defects. Consistent with the proposed role of the ANKS3 variant in the pathogenesis of the reported family's phenotype, we show that the mutant RNA failed to rescue the laterality defect in anks3 morphants compared to wild-type RNA. Furthermore, we describe a new mutant anks3 line that also displays laterality defect in the homozygous state. Our study suggests a role for ANKS3 in right-left axis determination in humans.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.affiliation: Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Toma Antonov
authors.initials: TA
authors.lastname: Yakulov
authors.affiliation: University Medical Centre Freiburg, Freiburg im Breisgau, Germany.
authors.forename: Amal
authors.initials: A
authors.lastname: Hashem
authors.affiliation: Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Gerd
authors.initials: G
authors.lastname: Walz
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
authors.forename: Fowzan S
authors.identifier: http://orcid.org/0000-0003-4158-341X
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002923:Cilia / Q000235:genetics* / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics; D059472:Exome / Q000235:genetics; D006331:Heart Diseases / Q000235:genetics* / Q000473:pathology; D059446:Heterotaxy Syndrome / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development*
chemical_list: C000595708:ANKS3 protein, human; D002352:Carrier Proteins