10.3389/fgene.2019.00800.s007
Lord J.J. Gowans
Lord J.J.
Gowans
Sophia Cameron-Christie
Sophia
Cameron-Christie
Rebecca L. Slayton
Rebecca L.
Slayton
Tamara Busch
Tamara
Busch
Miguel Romero-Bustillos
Miguel
Romero-Bustillos
Steven Eliason
Steven
Eliason
Mason Sweat
Mason
Sweat
Nara Sobreira
Nara
Sobreira
Wenjie Yu
Wenjie
Yu
Piranit N. Kantaputra
Piranit N.
Kantaputra
Elizabeth Wohler
Elizabeth
Wohler
Wasiu Lanre Adeyemo
Wasiu Lanre
Adeyemo
Salil A. Lachke
Salil A.
Lachke
Deepti Anand
Deepti
Anand
Collen Campbell
Collen
Campbell
Bernadette K. Drummond
Bernadette K.
Drummond
David M. Markie
David M.
Markie
W. Jansen van Vuuren
W. Jansen
van Vuuren
L. Jansen van Vuuren
L. Jansen
van Vuuren
Paul S. Casamassimo
Paul S.
Casamassimo
Ronald Ettinger
Ronald
Ettinger
Arwa Owais
Arwa
Owais
I. van Staden
I.
van Staden
Brad A. Amendt
Brad A.
Amendt
Adebowale A. Adeyemo
Adebowale A.
Adeyemo
Jeffrey C. Murray
Jeffrey C.
Murray
Stephen P. Robertson
Stephen P.
Robertson
Azeez Butali
Azeez
Butali
Image_7_Missense Pathogenic variants in KIF4A Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus.tif
Frontiers
2019
exome sequencing
X-linked recessive
microdontia
taurodontism
dens invaginatus
2019-09-20 16:11:45
Figure
https://frontiersin.figshare.com/articles/figure/Image_7_Missense_Pathogenic_variants_in_KIF4A_Affect_Dental_Morphogenesis_Resulting_in_X-linked_Taurodontism_Microdontia_and_Dens-Invaginatus_tif/9886040
<p>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.</p>