Journal article
Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus
Frontiers in genetics, Vol.10, pp.800-800
09/20/2019
DOI: 10.3389/fgene.2019.00800
PMCID: PMC6764483
PMID: 31616463
Abstract
The etiology of dental anomalies is multifactorial; and genetic and environmental factors that affect the dental lamina have been implicated. We investigated two families of European ancestry in which males were affected by taurodontism, microdontia and dens invaginatus. In both families, males were related to each other
via
unaffected females. A linkage analysis was conducted in a New Zealand family, followed by exome sequencing and focused analysis of the X-chromosome. In a US family, exome sequencing of the X-chromosome was followed by Sanger sequencing to conduct segregation analyses. We identified two independent missense variants in
KIF4A
that segregate in affected males and female carriers. The variant in a New Zealand family (p.Asp371His) predicts the substitution of a residue in the motor domain of the protein while the one in a US family (p.Arg771Lys) predicts the substitution of a residue in the domain that interacts with Protein Regulator of Cytokinesis 1 (PRC1). We demonstrated that the gene is expressed in the developing tooth bud during development, and that the p.Arg771Lys variant influences cell migration in an
in vitro
assay. These data implicate missense variations in
KIF4A
in a pathogenic mechanism that causes taurodontism, microdontia and dens invaginatus phenotypes.
Details
- Title: Subtitle
- Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus
- Creators
- Lord J.J. Gowans - Kwame Nkrumah University of Science and TechnologySophia Cameron-Christie - University of OtagoRebecca L. Slayton - University of WashingtonTamara Busch - University of IowaMiguel Romero-Bustillos - University of IowaSteven Eliason - University of IowaMason Sweat - University of IowaNara Sobreira - Johns Hopkins UniversityWenjie Yu - University of IowaPiranit N. Kantaputra - Chiang Mai UniversityElizabeth Wohler - Johns Hopkins UniversityWasiu Lanre Adeyemo - University of LagosSalil A. Lachke - University of DelawareDeepti Anand - University of DelawareCollen Campbell - University of IowaBernadette K. Drummond - University of OtagoDavid M. Markie - University of OtagoW. Jansen van Vuuren - , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,L. Jansen van Vuuren - University of OtagoPaul S. Casamassimo - The Ohio State UniversityRonald Ettinger - University of IowaArwa Owais - University of IowaI. van Staden - University of OtagoBrad A. Amendt - University of IowaAdebowale A. Adeyemo - National Human Genome Research InstituteJeffrey C. Murray - University of IowaStephen P. Robertson - University of OtagoAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in genetics, Vol.10, pp.800-800
- DOI
- 10.3389/fgene.2019.00800
- PMID
- 31616463
- PMCID
- PMC6764483
- NLM abbreviation
- Front Genet
- ISSN
- 1664-8021
- eISSN
- 1664-8021
- Publisher
- Frontiers Media S.A
- Grant note
- 72429 / Robert Wood Johnson Foundation DE022378 / National Institute of Dental and Craniofacial Research
- Language
- English
- Date published
- 09/20/2019
- Academic Unit
- Orthodontics; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Prosthodontics; Cardiovascular Medicine; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984284452702771
Metrics
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