0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      MYT1 role in the microtia‐craniofacial microsomia spectrum

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Craniofacial microsomia (CFM), also known as the oculo‐auriculo‐vertebral spectrum, comprises a variable phenotype with the most common features including microtia and mandibular hypoplasia on one or both sides, in addition to lateral oral clefts, epibulbar dermoids, cardiac, vertebral, and renal abnormalities. The etiology of CFM is largely unknown. The MYT1 gene has been reported as a candidate based in mutations found in three unrelated individuals. Additional patients with mutations in this gene are required to establish its causality. We present two individuals with CFM that have rare variants in MYT1 contributing to better understand the genotype and phenotype associated with mutations in this gene.

          Methods/Results

          We conducted genetic analysis using whole‐exome and ‐genome sequencing in 128 trios with CFM. Two novel MYT1 mutations were identified in two participants. Sanger sequencing was used to confirm these mutations.

          Conclusion

          We identified two additional individuals with CFM who carry rare variants in MYT1, further supporting the presumptive role of this gene in the CFM spectrum.

          Abstract

          We conducted genetic analysis using whole‐exome and ‐genome sequencing in 128 trios with CFM. Two novel MYT1 mutations were identified in two participants, further supporting the presumptive role of this gene in the CFM spectrum.

          Related collections

          Most cited references13

          • Record: found
          • Abstract: found
          • Article: not found

          Oculo-auriculo-vertebral spectrum: a review of the literature and genetic update.

          Oculo-auriculo-vertebral spectrum (OAVS, OMIM 164 210) is a developmental disorder primarily involving structures derived from the first and second pharyngeal arches during embryogenesis. The phenotype is clinically heterogeneous and is typically characterised by abnormal development of the ear, mandible anomalies and defects of the vertebral column. OAVS may occur as a multiple congenital abnormality, and associated findings include anomalies of the eye, brain, heart, kidneys and other organs and systems. Both genetic and environmental factors are thought to contribute to this craniofacial condition, however, the mechanisms are still poorly understood. Here, we present a review of the literature on OAVS, discussing what is known about the aetiology, candidate loci, possible mechanisms and the range of clinical features that characterise this condition. We also comment on some important aspects of recurrence risk counselling to aid clinical management.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Genome-wide occupancy links Hoxa2 to Wnt–β-catenin signaling in mouse embryonic development

            The regulation of gene expression is central to developmental programs and largely depends on the binding of sequence-specific transcription factors with cis-regulatory elements in the genome. Hox transcription factors specify the spatial coordinates of the body axis in all animals with bilateral symmetry, but a detailed knowledge of their molecular function in instructing cell fates is lacking. Here, we used chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) to identify Hoxa2 genomic locations in a time and space when it is actively instructing embryonic development in mouse. Our data reveals that Hoxa2 has large genome coverage and potentially regulates thousands of genes. Sequence analysis of Hoxa2-bound regions identifies high occurrence of two main classes of motifs, corresponding to Hox and Pbx–Hox recognition sequences. Examination of the binding targets of Hoxa2 faithfully captures the processes regulated by Hoxa2 during embryonic development; in addition, it uncovers a large cluster of potential targets involved in the Wnt-signaling pathway. In vivo examination of canonical Wnt–β-catenin signaling reveals activity specifically in Hoxa2 domain of expression, and this is undetectable in Hoxa2 mutant embryos. The comprehensive mapping of Hoxa2-binding sites provides a framework to study Hox regulatory networks in vertebrate developmental processes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis

              Summary The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.
                Bookmark

                Author and article information

                Contributors
                Daniela.luquetti@seattlechildrens.org
                Journal
                Mol Genet Genomic Med
                Mol Genet Genomic Med
                10.1002/(ISSN)2324-9269
                MGG3
                Molecular Genetics & Genomic Medicine
                John Wiley and Sons Inc. (Hoboken )
                2324-9269
                01 September 2020
                October 2020
                : 8
                : 10 ( doiID: 10.1002/mgg3.v8.10 )
                : e1401
                Affiliations
                [ 1 ] University of Washington School of Medicine Seattle WA USA
                [ 2 ] Seattle Children's Research Institute Seattle WA USA
                [ 3 ] Human Genomics Institute Pontificia Universidad Javeriana Bogotá Colombia
                [ 4 ] Hospital Universitario San Ignacio Bogotá Colombia
                [ 5 ] Universidad Icesi Cali Colombia
                [ 6 ] Clinica Comfamiliar Risaralda Pereira Colombia
                [ 7 ] Hospital Edgardo Rebagliati Martins Lima Peru
                [ 8 ] Pontificia Universidad Javeriana Cali Colombia
                Author notes
                [*] [* ] Correspondence

                Daniela V. Luquetti, 1900 9th avenue C9S-5, Seattle, WA, USA.

                Email: Daniela.luquetti@ 123456seattlechildrens.org

                Author information
                https://orcid.org/0000-0001-6059-7708
                Article
                MGG31401
                10.1002/mgg3.1401
                7549594
                32871052
                2bd35519-842f-4f16-8d89-90a7b74a1900
                © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 09 June 2020
                : 23 June 2020
                Page count
                Figures: 1, Tables: 2, Pages: 5, Words: 6726
                Funding
                Funded by: National Institute on Deafness and Other Communication Disorders
                Award ID: R00DC011282
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development , open-funder-registry 10.13039/100009633;
                Award ID: X01HL140518‐01
                Funded by: National Institute of Dental and Craniofacial Research , open-funder-registry 10.13039/100000072;
                Award ID: R01DE022438
                Award ID: RC1DE020270
                Categories
                Clinical Report
                Clinical Reports
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.2 mode:remove_FC converted:12.10.2020

                craniofacial microsomia,genetics,hemifacial microsomia,microtia,oculo‐auriculo‐vertebral spectrum

                Comments

                Comment on this article