Abstract
Approximately 3% of the live-born infants have major dysmorphic features, and about two-thirds of which are observed in the maxillofacial region; however, in many cases, the etiology of the dysmorphic features remains uncertain. Recently, the genome-wide screening of large patient cohorts with congenital disorders has made it possible to discover genomic aberrations corresponding to the pathogenesis. In our analyses of more than 536 cases of clinically undiagnosed multiple congenital anomalies and mental retardation (MR) by microarray-based comparative genomic hybridization, we detected two non-consanguineous unrelated patients with microdeletions at 10p11.23-p12.1, which overlapped for 957 kb, including four protein-coding genes: ARMC4, MPP7, WAC and BAMBI. As the two patients had similar phenotypes; for example, MR and multiple maxillofacial abnormalities including midface retrusion, wide mouth and large tongue, we assessed the phenotypes in detail to define the common features, using quantitative evaluations of the maxillofacial dysmorphism. The concordance of the genetic and phenotypic alterations is a good evidence of a new syndrome. Although an interstitial deletion of 10p is rare, the current study is the first trial to examine precisely the craniofacial characteristics of patients with a heterozygous deletion at 10p11.23-p12.1, and presents good evidence to diagnose potential patients with the same genetic cause.
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Acknowledgements
This study was supported in part by Grants-in-Aid for Scientific Research and Scientific Research on Priority Areas, and a Global Center of Excellence (GCOE) Program for International Research Center for Molecular Science in Tooth and Bone Diseases from the Ministry of Education, Culture, Sports, Science and Technology, Japan; a Health and Labour Sciences Research Grant by the Ministry of Health, Labour and Welfare, Japan; and a grant from the New Energy and Industrial Technology Development Organization (NEDO). We are grateful to Ayako Takahashi and Rumi Mori for technical assistance.
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UCSC Genome Bowser, March 2006 build (NCBI36/hg18), http://genome.ucsc.edu/
Database of Genome Variation (Nov. 02, 2010), http://projects.tcag.ca/variation/
Segmental Duplication Database, http://projects.tcag.ca/humandup/
Segmental Duplication Database, http://humanparalogy.gs.washington.edu/.
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Okamoto, N., Hayashi, S., Masui, A. et al. Deletion at chromosome 10p11.23-p12.1 defines characteristic phenotypes with marked midface retrusion. J Hum Genet 57, 191–196 (2012). https://doi.org/10.1038/jhg.2011.154
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DOI: https://doi.org/10.1038/jhg.2011.154
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