ANKS3 is mutated in a family with autosomal recessive laterality defect.
PMID 27417436 | DOI 10.1007/s00439-016-1712-4 · Human genetics · 2016
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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | ANKS3 | “ANKS3 is mutated in a family with autosomal recessive laterality defect.” | 0.98 | hgnc_dict_v1 |
| phenotype | congenital heart disease | “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.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Population | “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.” | 0.80 | saudi_context_rules_v1 |