Expanding the oro-dental and mutational spectra of kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs

Thantrira Porntaveetus; Mushriq F. Abid; Thanakorn Theerapanon; Chalurmpon Srichomthong; Atsushi Ohazama; Katsushige Kawasaki; Maiko Kawasaki; Kanya Suphapeetiporn; Paul T. Sharpe; Vorasuk Shotelersuk

doi:10.7150/ijbs.23517

Expanding the oro-dental and mutational spectra of kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs

Thantrira Porntaveetus^*, Mushriq F. Abid, Thanakorn Theerapanon, Chalurmpon Srichomthong, Atsushi Ohazama, Katsushige Kawasaki, Maiko Kawasaki, Kanya Suphapeetiporn, Paul T. Sharpe, Vorasuk Shotelersuk

^*Corresponding author for this work

Centre for Craniofacial & Regenerative Biology

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

219 Downloads (Pure)

Abstract

Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size. Exome sequencing successfully identified that six patients were heterozygous for mutations in KMT2D, and one in KDM6A. Six were novel mutations, of which five were in KMT2D and one in KDM6A. They were truncating mutations including four frameshift deletions and two nonsense mutations. The predicted non-functional KMT2D and KDM6A proteins are expected to cause disease by haploinsufficiency. Our study expands oro-dental, medical, and mutational spectra associated with Kabuki syndrome. We also demonstrate for the first time that KMT2D and KDM6A are expressed in the dental epithelium of human tooth germs.

Original language	English
Pages (from-to)	381-389
Number of pages	9
Journal	International Journal of Biological Sciences
Volume	14
Issue number	4
DOIs	https://doi.org/10.7150/ijbs.23517
Publication status	Published - 9 Mar 2018

Keywords

Craniofacial anomalies
Genetics
Hypodontia
Tooth development

Access to Document

10.7150/ijbs.23517Licence: CC BY-NC

Expanding the Oro-Dental_PORNTAVEETUS_Published9March2018_GOLD VoR (CC BY-NC)Final published version, 2.03 MBLicence: CC BY-NC

Cite this

Porntaveetus, T., Abid, M. F., Theerapanon, T., Srichomthong, C., Ohazama, A., Kawasaki, K., Kawasaki, M., Suphapeetiporn, K., Sharpe, P. T., & Shotelersuk, V. (2018). Expanding the oro-dental and mutational spectra of kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs. International Journal of Biological Sciences, 14(4), 381-389. https://doi.org/10.7150/ijbs.23517

@article{f58cec66f1c94fd99e030294ad4ff8b9,

title = "Expanding the oro-dental and mutational spectra of kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs",

abstract = "Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size. Exome sequencing successfully identified that six patients were heterozygous for mutations in KMT2D, and one in KDM6A. Six were novel mutations, of which five were in KMT2D and one in KDM6A. They were truncating mutations including four frameshift deletions and two nonsense mutations. The predicted non-functional KMT2D and KDM6A proteins are expected to cause disease by haploinsufficiency. Our study expands oro-dental, medical, and mutational spectra associated with Kabuki syndrome. We also demonstrate for the first time that KMT2D and KDM6A are expressed in the dental epithelium of human tooth germs.",

keywords = "Craniofacial anomalies, Genetics, Hypodontia, Tooth development",

author = "Thantrira Porntaveetus and Abid, {Mushriq F.} and Thanakorn Theerapanon and Chalurmpon Srichomthong and Atsushi Ohazama and Katsushige Kawasaki and Maiko Kawasaki and Kanya Suphapeetiporn and Sharpe, {Paul T.} and Vorasuk Shotelersuk",

year = "2018",

month = mar,

day = "9",

doi = "10.7150/ijbs.23517",

language = "English",

volume = "14",

pages = "381--389",

journal = "International Journal of Biological Sciences",

issn = "1449-2288",

publisher = "Ivyspring International Publisher",

number = "4",

}

Porntaveetus, T, Abid, MF, Theerapanon, T, Srichomthong, C, Ohazama, A, Kawasaki, K, Kawasaki, M, Suphapeetiporn, K, Sharpe, PT & Shotelersuk, V 2018, 'Expanding the oro-dental and mutational spectra of kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs', International Journal of Biological Sciences, vol. 14, no. 4, pp. 381-389. https://doi.org/10.7150/ijbs.23517

TY - JOUR

T1 - Expanding the oro-dental and mutational spectra of kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs

AU - Porntaveetus, Thantrira

AU - Abid, Mushriq F.

AU - Theerapanon, Thanakorn

AU - Srichomthong, Chalurmpon

AU - Ohazama, Atsushi

AU - Kawasaki, Katsushige

AU - Kawasaki, Maiko

AU - Suphapeetiporn, Kanya

AU - Sharpe, Paul T.

AU - Shotelersuk, Vorasuk

PY - 2018/3/9

Y1 - 2018/3/9

N2 - Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size. Exome sequencing successfully identified that six patients were heterozygous for mutations in KMT2D, and one in KDM6A. Six were novel mutations, of which five were in KMT2D and one in KDM6A. They were truncating mutations including four frameshift deletions and two nonsense mutations. The predicted non-functional KMT2D and KDM6A proteins are expected to cause disease by haploinsufficiency. Our study expands oro-dental, medical, and mutational spectra associated with Kabuki syndrome. We also demonstrate for the first time that KMT2D and KDM6A are expressed in the dental epithelium of human tooth germs.

AB - Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of KMT2D (histone-lysine N-methyltransferase 2D) or KDM6A (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size. Exome sequencing successfully identified that six patients were heterozygous for mutations in KMT2D, and one in KDM6A. Six were novel mutations, of which five were in KMT2D and one in KDM6A. They were truncating mutations including four frameshift deletions and two nonsense mutations. The predicted non-functional KMT2D and KDM6A proteins are expected to cause disease by haploinsufficiency. Our study expands oro-dental, medical, and mutational spectra associated with Kabuki syndrome. We also demonstrate for the first time that KMT2D and KDM6A are expressed in the dental epithelium of human tooth germs.

KW - Craniofacial anomalies

KW - Genetics

KW - Hypodontia

KW - Tooth development

UR - http://www.scopus.com/inward/record.url?scp=85045193269&partnerID=8YFLogxK

U2 - 10.7150/ijbs.23517

DO - 10.7150/ijbs.23517

M3 - Article

AN - SCOPUS:85045193269

SN - 1449-2288

VL - 14

SP - 381

EP - 389

JO - International Journal of Biological Sciences

JF - International Journal of Biological Sciences

IS - 4

ER -

Expanding the oro-dental and mutational spectra of kabuki syndrome and expression of KMT2D and KDM6A in human tooth germs

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this