Disruption of ALX1 Causes Extreme Microphthalmia and Severe Facial Clefting: Expanding the Spectrum of Autosomal-Recessive ALX-Related Frontonasal Dysplasia

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dc.contributor.authorUz, Elif
dc.contributor.authorAlanay, Yasemin
dc.contributor.authorAktas, Dilek
dc.contributor.authorVargel, İbrahim
dc.contributor.authorGücer, Şafak
dc.contributor.authorTunçbilek, Gökhan
dc.contributor.authorAkarsu, Nurten A.
dc.date.accessioned2020-06-25T17:51:14Z
dc.date.available2020-06-25T17:51:14Z
dc.date.issued2010
dc.departmentKırıkkale Üniversitesi
dc.descriptionYILMAZ, Engin/0000-0001-8873-7645; Akarsu, Nurten/0000-0001-5432-0032; Ozdag, Hilal/0000-0001-7940-2499; Liehr, Thomas/0000-0003-1672-3054; Alanay, Yasemin/0000-0003-0683-9731; von Eggeling, Ferdinand/0000-0002-8062-6999
dc.description.abstractWe present an autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this clinical entity to chromosome 12q21. In one of the families, three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.7 Mb deletion containing the ALX1 (CART1) gene, which encodes the aristaless-like homeobox 1 transcription factor. In the second family we identified a homozygous donor-splice-site mutation (c.531+1G > A) in the ALX1 gene, providing evidence that complete loss of function of ALX1 protein causes severe disruption of early craniofacial development. Unlike loss of its murine ortholog, loss of human ALX1 does not result in neural-tube defects; however, it does severely affect the orchestrated fusion between frontonasal, nasomedial, nasolateral, and maxillary processes during early-stage embryogenesis. This study further expands the spectrum of the recently recognized autosomal-recessive ALX-related FND phenotype in humans.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [108S420]; European Research Area Network (E-RARE) [R07197KS]en_US
dc.description.sponsorshipWe are grateful to the families for their participation in the study. We thank Han Brunner for critical reading and comments, Ebru Oralli Bircan for illustrations, Hacettepe University Craniofacial Surgery Study Group members Yucel Erk, Emin Mavili, Aycan Kayikcioglu (Plastic and Reconstructive Surgery), Kemal Benli (Neurosurgery), Aysenur Cila (Radiology), Tulin Taner, and liken Kocadereli (Orthodonty) for evaluating the frontonasal malformation cases in the registry. This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) (grant numbers 108S420 to N.A.A), and the overall consortium (CRANIRARE) was supported by the European Research Area Network (E-RARE) (project number R07197KS).en_US
dc.identifier.citationUz, E., Alanay, Y., Aktas, D., Vargel, I., Gucer, S., Tuncbilek, G., von Eggeling, F., Yilmaz, E., Deren, O., Posorski, N., Ozdag, H., Liehr, T., Balci, S., Alikasifoglu, M., Wollnik, B., & Akarsu, N. A. (2010). Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia. American journal of human genetics, 86(5), 789–796. https://doi.org/10.1016/j.ajhg.2010.04.002en_US
dc.identifier.doi10.1016/j.ajhg.2010.04.002
dc.identifier.endpage796en_US
dc.identifier.issn0002-9297
dc.identifier.issn1537-6605
dc.identifier.issue5en_US
dc.identifier.pmid20451171
dc.identifier.scopus2-s2.0-77951976826
dc.identifier.scopusqualityQ1
dc.identifier.startpage789en_US
dc.identifier.urihttps://doi.org/10.1016/j.ajhg.2010.04.002
dc.identifier.urihttps://hdl.handle.net/20.500.12587/4744
dc.identifier.volume86en_US
dc.identifier.wosWOS:000278045300015
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherCell Pressen_US
dc.relation.ispartofAmerican Journal Of Human Genetics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleDisruption of ALX1 Causes Extreme Microphthalmia and Severe Facial Clefting: Expanding the Spectrum of Autosomal-Recessive ALX-Related Frontonasal Dysplasiaen_US
dc.typeArticle

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