Whole-genome sequencing in a pair of monozygotic twins with discordant cleft lip and palate subtypes.

Abstract:

OBJECTIVE:Orofacial clefts (OFCs) are common and etiologically complex birth defects. This study explored potential genetic differences in a pair of Japanese monozygotic (MZ) twins with different forms of OFC using whole-genome sequencing. SUBJECTS AND METHODS:One co-twin (MZ-1) presented with nonsyndromic bilateral cleft lip and palate; the other co-twin (MZ-2) had nonsyndromic bilateral cleft lip and unilateral left-sided cleft alveolus. Neither parent had an OFC. Craniofacial morphologic features and potential genetic differences were compared using standard cephalometry and whole-genome sequencing, respectively. RESULTS:Morphologically, MZ-1 had a smaller vertical mandibular height, compared to MZ-2. However, no discordant genetic differences were detected. Moreover, both twins and their parents harbored rare candidate gene variants (GRHL3; TPM1) considered to be associated with OFCs. CONCLUSION:The observed differences between MZ-1 and MZ-2 in craniofacial morphology assessed by cephalograms might be directly attributable to the effects of the OFC on growth and/or differences in surgical history, given the lack of any differences in genetic background. However, comparisons of discordant MZ twins should continue to identify novel candidates that might control OFC or that might partly explain the missing heritability for this common birth defect, in addition to understanding craniofacial growth and development.

journal_name

Oral Dis

journal_title

Oral diseases

authors

Takahashi M,Hosomichi K,Yamaguchi T,Nagahama R,Yoshida H,Maki K,Marazita ML,Weinberg SM,Tajima A

doi

10.1111/odi.12910

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

1303-1309

issue

7

eissn

1354-523X

issn

1601-0825

journal_volume

24

pub_type

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