Quantitative Craniofacial Analysis and Generation of Human Induced Pluripotent Stem Cells for Muenke Syndrome: A Case Report.

Autor: Kidwai FK; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Mui BWH; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Almpani K; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Jani P; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Keyvanfar C; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Iqbal K; School of Dental Medicine, Tufts University, Boston, MA 02111, USA., Paravastu SS; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Arora D; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.; Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA., Orzechowski P; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Merling RK; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Mallon B; NIH Stem Cell Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Myneni VD; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Ahmad M; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Kruszka P; National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Muenke M; National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Woodcock J; Materials Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA., Gilman JW; Materials Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20899, USA., Robey PG; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA., Lee JS; National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.; Craniofacial Anomalies & Regeneration Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Jazyk: angličtina
Zdroj: Journal of developmental biology [J Dev Biol] 2021 Sep 22; Vol. 9 (4). Date of Electronic Publication: 2021 Sep 22.
DOI: 10.3390/jdb9040039
Abstrakt: In this case report, we focus on Muenke syndrome (MS), a disease caused by the p.Pro250Arg variant in fibroblast growth factor receptor 3 (FGFR3) and characterized by uni- or bilateral coronal suture synostosis, macrocephaly without craniosynostosis, dysmorphic craniofacial features, and dental malocclusion. The clinical findings of MS are further complicated by variable expression of phenotypic traits and incomplete penetrance. As such, unraveling the mechanisms behind MS will require a comprehensive and systematic way of phenotyping patients to precisely identify the impact of the mutation variant on craniofacial development. To establish this framework, we quantitatively delineated the craniofacial phenotype of an individual with MS and compared this to his unaffected parents using three-dimensional cephalometric analysis of cone beam computed tomography scans and geometric morphometric analysis, in addition to an extensive clinical evaluation. Secondly, given the utility of human induced pluripotent stem cells (hiPSCs) as a patient-specific investigative tool, we also generated the first hiPSCs derived from a family trio, the proband and his unaffected parents as controls, with detailed characterization of all cell lines. This report provides a starting point for evaluating the mechanistic underpinning of the craniofacial development in MS with the goal of linking specific clinical manifestations to molecular insights gained from hiPSC-based disease modeling.
Databáze: MEDLINE