OTX2 duplication is implicated in hemifacial microsomia.

Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. We investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. Whole-exome sequencing results indica...

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Autores principales:	Dina Zielinski, Barak Markus, Mona Sheikh, Melissa Gymrek, Clement Chu, Marta Zaks, Balaji Srinivasan, Jodi D Hoffman, Dror Aizenbud, Yaniv Erlich
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3962f316f8ce4b5fb35f0fb513947cd5
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spelling	oai:doaj.org-article:3962f316f8ce4b5fb35f0fb513947cd52021-11-18T08:19:55ZOTX2 duplication is implicated in hemifacial microsomia.1932-620310.1371/journal.pone.0096788https://doaj.org/article/3962f316f8ce4b5fb35f0fb513947cd52014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24816892/?tool=EBIhttps://doaj.org/toc/1932-6203Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. We investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. Whole-exome sequencing results indicated the absence of a pathogenic coding point mutation. A genome-wide survey of segmental variations identified a 1.3 Mb duplication of chromosome 14q22.3 in all affected individuals that was absent in more than 1000 chromosomes of ethnically matched controls. The duplication was absent in seven additional sporadic HFM cases, which is consistent with the known heterogeneity of the disorder. To find the critical gene in the duplicated region, we analyzed signatures of human craniofacial disease networks, mouse expression data, and predictions of dosage sensitivity. All of these approaches implicated OTX2 as the most likely causal gene. Moreover, OTX2 is a known oncogenic driver in medulloblastoma, a condition that was diagnosed in the proband during the course of the study. Our findings suggest a role for OTX2 dosage sensitivity in human craniofacial development and raise the possibility of a shared etiology between a subtype of hemifacial microsomia and medulloblastoma.Dina ZielinskiBarak MarkusMona SheikhMelissa GymrekClement ChuMarta ZaksBalaji SrinivasanJodi D HoffmanDror AizenbudYaniv ErlichPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e96788 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dina Zielinski Barak Markus Mona Sheikh Melissa Gymrek Clement Chu Marta Zaks Balaji Srinivasan Jodi D Hoffman Dror Aizenbud Yaniv Erlich OTX2 duplication is implicated in hemifacial microsomia.
description	Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. We investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. Whole-exome sequencing results indicated the absence of a pathogenic coding point mutation. A genome-wide survey of segmental variations identified a 1.3 Mb duplication of chromosome 14q22.3 in all affected individuals that was absent in more than 1000 chromosomes of ethnically matched controls. The duplication was absent in seven additional sporadic HFM cases, which is consistent with the known heterogeneity of the disorder. To find the critical gene in the duplicated region, we analyzed signatures of human craniofacial disease networks, mouse expression data, and predictions of dosage sensitivity. All of these approaches implicated OTX2 as the most likely causal gene. Moreover, OTX2 is a known oncogenic driver in medulloblastoma, a condition that was diagnosed in the proband during the course of the study. Our findings suggest a role for OTX2 dosage sensitivity in human craniofacial development and raise the possibility of a shared etiology between a subtype of hemifacial microsomia and medulloblastoma.
format	article
author	Dina Zielinski Barak Markus Mona Sheikh Melissa Gymrek Clement Chu Marta Zaks Balaji Srinivasan Jodi D Hoffman Dror Aizenbud Yaniv Erlich
author_facet	Dina Zielinski Barak Markus Mona Sheikh Melissa Gymrek Clement Chu Marta Zaks Balaji Srinivasan Jodi D Hoffman Dror Aizenbud Yaniv Erlich
author_sort	Dina Zielinski
title	OTX2 duplication is implicated in hemifacial microsomia.
title_short	OTX2 duplication is implicated in hemifacial microsomia.
title_full	OTX2 duplication is implicated in hemifacial microsomia.
title_fullStr	OTX2 duplication is implicated in hemifacial microsomia.
title_full_unstemmed	OTX2 duplication is implicated in hemifacial microsomia.
title_sort	otx2 duplication is implicated in hemifacial microsomia.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3962f316f8ce4b5fb35f0fb513947cd5
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OTX2 duplication is implicated in hemifacial microsomia.

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