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Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus.
Front Genet. 2019; 10:800.FG

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.

Authors+Show Affiliations

Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.Department of Pediatric Dentistry, University of Washington, Seattle, WA, United States.Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, United States.Department of Anatomy, University of Iowa, Iowa City, IA, United States.Department of Anatomy, University of Iowa, Iowa City, IA, United States.Department of Anatomy, University of Iowa, Iowa City, IA, United States.Institute of Genetic Medicine, John Hopkins University, Baltimore, MD, United States.Department of Anatomy, University of Iowa, Iowa City, IA, United States.Center of Excellence in Medical Genetics Research, Chiang Mai University, Chiang Mai, Thailand. Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.Institute of Genetic Medicine, John Hopkins University, Baltimore, MD, United States.Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria.Department of Biological Sciences, University of Delaware, Newark, DE, United States.Department of Biological Sciences, University of Delaware, Newark, DE, United States.Department of Internal Medicine, University of Iowa, Iowa City, IA, United States.Department of Oral Sciences, University of Otago, Dunedin, New Zealand.Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.Department of Oral Sciences, University of Otago, Dunedin, New Zealand.Department of Oral Sciences, University of Otago, Dunedin, New Zealand.Department of Pediatric Dentistry, Ohio State University, Columbus, OH, United States.Department of Prosthodontics, University of Iowa, Iowa City, IA, United States.Department of Pediatric Dentistry, College of Dentistry, University of Iowa, Iowa City, IA, United States.Department of Oral Sciences, University of Otago, Dunedin, New Zealand.Department of Anatomy, University of Iowa, Iowa City, IA, United States.National Human Genomic Research Institute, Bethesda, MD, United States.Department of Pediatrics University of Iowa, Iowa City, IA, United States.Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31616463

Citation

Gowans, Lord J J., et al. "Missense Pathogenic Variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus." Frontiers in Genetics, vol. 10, 2019, p. 800.
Gowans LJJ, Cameron-Christie S, Slayton RL, et al. Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus. Front Genet. 2019;10:800.
Gowans, L. J. J., Cameron-Christie, S., Slayton, R. L., Busch, T., Romero-Bustillos, M., Eliason, S., Sweat, M., Sobreira, N., Yu, W., Kantaputra, P. N., Wohler, E., Adeyemo, W. L., Lachke, S. A., Anand, D., Campbell, C., Drummond, B. K., Markie, D. M., van Vuuren, W. J., van Vuuren, L. J., ... Butali, A. (2019). Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus. Frontiers in Genetics, 10, 800. https://doi.org/10.3389/fgene.2019.00800
Gowans LJJ, et al. Missense Pathogenic Variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus. Front Genet. 2019;10:800. PubMed PMID: 31616463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus. AU - Gowans,Lord J J, AU - Cameron-Christie,Sophia, AU - Slayton,Rebecca L, AU - Busch,Tamara, AU - Romero-Bustillos,Miguel, AU - Eliason,Steven, AU - Sweat,Mason, AU - Sobreira,Nara, AU - Yu,Wenjie, AU - Kantaputra,Piranit N, AU - Wohler,Elizabeth, AU - Adeyemo,Wasiu Lanre, AU - Lachke,Salil A, AU - Anand,Deepti, AU - Campbell,Collen, AU - Drummond,Bernadette K, AU - Markie,David M, AU - van Vuuren,W Jansen, AU - van Vuuren,L Jansen, AU - Casamassimo,Paul S, AU - Ettinger,Ronald, AU - Owais,Arwa, AU - van Staden,I, AU - Amendt,Brad A, AU - Adeyemo,Adebowale A, AU - Murray,Jeffrey C, AU - Robertson,Stephen P, AU - Butali,Azeez, Y1 - 2019/09/20/ PY - 2018/12/17/received PY - 2019/07/30/accepted PY - 2019/10/17/entrez PY - 2019/10/17/pubmed PY - 2019/10/17/medline KW - X-linked recessive KW - dens invaginatus KW - exome sequencing KW - microdontia KW - taurodontism SP - 800 EP - 800 JF - Frontiers in genetics JO - Front Genet VL - 10 N2 - 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. SN - 1664-8021 UR - https://www.unboundmedicine.com/medline/citation/31616463/Missense_Pathogenic_variants_in_KIF4A_Affect_Dental_Morphogenesis_Resulting_in_X-linked_Taurodontism,_Microdontia_and_Dens-Invaginatus L2 - https://doi.org/10.3389/fgene.2019.00800 DB - PRIME DP - Unbound Medicine ER -
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