ArticleEuropean journal of human genetics : EJHG2018
Clinical and experimental evidence suggest a link between KIF7 and C5orf42-related ciliopathies through Sonic Hedgehog signaling.
Article in European journal of human genetics : EJHG, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Traffic Jams in the Brain: How Kinesin Dysfunction Shapes Neurodevelopmental Disorders.Current issues in molecular biology · 2026Review
- Primary cilia and neural computation.Journal of biomedical science · 2026Review
- Deciphering the role of tubulin's C-terminal tail in kinesin binding using computational and clustering approaches.Scientific reports · 2026Article
- Clinical, genetic and bioinformatic analysis of Saudi families with Joubert syndrome and related disorders.Human genomics · 2026Article
- Article
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
- Neuronal guidance behaviours: the primary cilium perspective.Frontiers in cell and developmental biology · 2025Review
- A cell-autonomous role for primary cilium-mediated signaling in long-range commissural axon guidance.Development (Cambridge, England) · 2024Article
- Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro.Cell and tissue research · 2024Article
- NovelOpen life sciences · 2023Article
- Long-Surviving Adult Siblings With Joubert Syndrome Harboring a Novel Compound HeterozygousNeurology. Genetics · 2022Article
- Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.International journal of molecular sciences · 2022Review
- Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components.Journal of cell science · 2022Article
- Genetic heterogeneity in corpus callosum agenesis.Frontiers in genetics · 2022Review
- Primary cilia in hard tissue development and diseases.Frontiers of medicine · 2021Review
- Smoothened and ARL13B are critical in mouse for superior cerebellar peduncle targeting.Genetics · 2021Article
- Sequences in the stalk domain regulate auto-inhibition and ciliary tip localization of the immotile kinesin-4 KIF7.Journal of cell science · 2021Article
- Clinical heterogeneity and intrafamilial variability of Joubert syndrome in two siblings with CPLANE1 variants.Molecular genetics & genomic medicine · 2021Article
- Investigating Primary Cilia during Peripheral Nervous System Formation.International journal of molecular sciences · 2021Article
- Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms.Brain sciences · 2020Review
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Authors and funding
25 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental disorder caused by KIF7 defects and belongs to the heterogeneous group of ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism, facial dysmorphism has not been emphasized in JBTS cohorts with molecular diagnosis. To evaluate the specificity and etiology of ACLS craniofacial features, we performed whole exome or targeted Sanger sequencing in patients with the aforementioned overlapping craniofacial appearance but variable additional ciliopathy features followed by functional studies. We found (likely) pathogenic variants of KIF7 in 5 out of 9 families, including the original ACLS patients, and delineated 1000 to 4000-year-old Swiss founder alleles. Three of the remaining families had (likely) pathogenic variants in the JBTS gene C5orf42, and one patient had a novel de novo frameshift variant in SHH known to cause autosomal dominant holoprosencephaly. In accordance with the patients' craniofacial anomalies, we showed facial midline widening after silencing of C5orf42 in chicken embryos. We further supported the link between KIF7, SHH, and C5orf42 by demonstrating abnormal primary cilia and diminished response to a SHH agonist in fibroblasts of C5orf42-mutated patients, as well as axonal pathfinding errors in C5orf42-silenced chicken embryos similar to those observed after perturbation of Shh signaling. Our findings, therefore, suggest that beside the neurodevelopmental features, macrocephaly and facial widening are likely more general signs of disturbed SHH signaling. Nevertheless, long-term follow-up revealed that C5orf42-mutated patients showed catch-up development and fainting of facial features contrary to KIF7-mutated patients.
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