Exploration of genetic factors determining cleft side in a pair of monozygotic twins with mirror-image cleft lip and palate using whole-genome sequencing and comparison of craniofacial morphology

Masahiro Takahashi; Kazuyoshi Hosomichi; Tetsutaro Yamaguchi; Ryo Nagahama; Hiroshi Yoshida; Mary L Marazita; Seth M Weinberg; Koutaro Maki; Atsushi Tajima

doi:10.1016/j.archoralbio.2018.08.009

Exploration of genetic factors determining cleft side in a pair of monozygotic twins with mirror-image cleft lip and palate using whole-genome sequencing and comparison of craniofacial morphology

Arch Oral Biol. 2018 Dec:96:33-38. doi: 10.1016/j.archoralbio.2018.08.009. Epub 2018 Aug 19.

Authors

Masahiro Takahashi¹, Kazuyoshi Hosomichi², Tetsutaro Yamaguchi³, Ryo Nagahama⁴, Hiroshi Yoshida⁴, Mary L Marazita⁵, Seth M Weinberg⁶, Koutaro Maki⁴, Atsushi Tajima²

Affiliations

¹ Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan. Electronic address: mtakahashi@dent.showa-u.ac.jp.
² Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Ishikawa, Japan.
³ Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan; Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
⁵ Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Clinical and Translational Science Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Anthropology, University of Pittsburgh, Pittsburgh, PA, USA.

PMID: 30172943
DOI: 10.1016/j.archoralbio.2018.08.009

Abstract

Objective: The aim of the present study is to explore genetic factors determining difference of cleft side using whole-genome sequencing and evaluation of craniofacial morphology using cephalometric analysis between Japanese monozygotic (MZ) twins with mirror-image cleft lip and palate (CLP).

Design: We selected a Japanese MZ twin pair (MZ-A and MZ-B) affected with unilateral CLP who are discordant for cleft side (left/right) and conducted whole-genome sequencing to identify genetic factors determining cleft side. Moreover, we compared their craniofacial morphologies using cephalograms.

Results: Whole-genome sequencing results suggested that no discordant DNA variants were found between MZ-A and MZ-B. The comparison of craniofacial morphology between the MZ twins revealed that MZ-B had maxillary deficiency and slightly more mandibular protrusion than MZ-A.

Conclusions: It is indicated that environmental factors might be a critical factor that influences the determination of difference of cleft side in orofacial clefts. In addition, we found some differences in craniofacial morphology between MZ-A and MZ-B. Our findings suggest that various environmental factors, such as epigenetics, might be a critical factor that influences the determination of difference of cleft side in CLP rather than inherited genetic factors.

Keywords: Cleft laterality; Cleft lip and palate; Craniofacial morphology; Mirror-image asymmetry; Monozygotic twin discordancy; Whole-genome sequencing.

Publication types

Case Reports

MeSH terms

Alleles
Cephalometry
Child, Preschool
Cleft Lip / genetics*
Cleft Palate / genetics*
Diseases in Twins / genetics*
Genotype
Humans
Japan
Male
Sequence Analysis, DNA
Twins, Monozygotic