Craniofacial ciliopathies: A new classification for craniofacial disorders

Brugmann, Samantha A.; Cordero, Dwight R.; Helms, Jill A.

doi:10.1002/ajmg.a.33727

Cited by 63 publications

(49 citation statements)

References 103 publications

(116 reference statements)

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“…Second, analysis of animal models suggests that a variety of developmental disorders, including craniofacial dysmorphology, result from defects in ciliary function (Huber and Cormier-Daire, 2012). Finally, advances in clinical genomics have improved annotation of disease alleles, subsequently identifying numerous, unclassified syndromes as ciliopathies (Brugmann et al., 2010). The challenge now is understanding how these seemingly heterogeneous disorders arise (Novarino et al., 2011), and our data suggest that commonalities in phenotype are likely to reflect shared signaling events, which converge into shared phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

et al. 2013

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SummaryCiliopathies are a broad class of human disorders with craniofacial dysmorphology as a common feature. Among these is high arched palate, a condition that affects speech and quality of life. Using the ciliopathic Fuz mutant mouse, we find that high arched palate does not, as commonly suggested, arise from midface hypoplasia. Rather, increased neural crest expands the maxillary primordia. In Fuz mutants, this phenotype stems from dysregulated Gli processing, which in turn results in excessive craniofacial Fgf8 gene expression. Accordingly, genetic reduction of Fgf8 ameliorates the maxillary phenotypes. Similar phenotypes result from mutation of oral-facial-digital syndrome 1 (Ofd1), suggesting that aberrant transcription of Fgf8 is a common feature of ciliopathies. High arched palate is also a prevalent feature of fibroblast growth factor (FGF) hyperactivation syndromes. Thus, our findings elucidate the etiology for a common craniofacial anomaly and identify links between two classes of human disease: FGF-hyperactivation syndromes and ciliopathies.

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Section: Discussionmentioning

confidence: 99%

Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

et al. 2013

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“…As mentioned above, cilia play important roles during craniofacial development by serving as a hub for signaling regulation [123, 124]. Growth factor signaling pathways also play roles for cilial function, thus malfunction of the signaling components may potentially lead ciliopathy.…”

Section: Ciliopathymentioning

confidence: 99%

Neural crest cell signaling pathways critical to cranial bone development and pathology

Mishina

Snider

2014

Experimental Cell Research

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Neural crest cells appear early during embryogenesis and give rise to many structures in the mature adult. In particular, a specific population of neural crest cells migrates to and populates developing cranial tissues. The ensuing differentiation of these cells via individually complex and often intersecting signaling pathways is indispensible to growth and development of the craniofacial complex. Much research has been devoted to this area of development with particular emphasis on cell signaling events required for physiologic development. Understanding such mechanisms will allow researchers to investigate ways in which they can be exploited in order to treat a multitude of diseases affecting the craniofacial complex. Knowing how these multipotent cells are driven towards distinct fates could, in due course, allow patients to receive regenerative therapies for tissues lost to a variety of pathologies. In order to realize this goal, nucleotide sequencing advances allowing snapshots of entire genomes and exomes are being utilized to identify molecular entities associated with disease states. Once identified, these entities can be validated for biological significance with other methods. A crucial next step is the integration of knowledge gleaned from observations in disease states with normal physiology to generate an explanatory model for craniofacial development. This review seeks to provide a current view of the landscape on cell signaling and fate determination of the neural crest and to provide possible avenues of approach for future research.

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“…Their analysis was based on screening for (multiple) classic ciliopathy features in the Online Mendelian Inheritance in Man (OMIM) clinical database. Besides comparing human phenotypes, we can also extract predictive markers for human disease from studies with mouse mutants; there are for instance clues from a conditional murine Kif3a mutant that frontonasal dysplasia could be the result of ciliary dysfunction [70–72]. Finally, identification of novel ciliary functions for proteins associated with human disease may reveal that the molecular cause of disease may be (in part) due to ciliary disruption, thereby opening avenues for development of targeted therapies.…”

Section: New Ciliopathiesmentioning

confidence: 99%

Current insights into renal ciliopathies: what can genetics teach us?

Arts

Knoers

2012

Pediatr Nephrol

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Ciliopathies are a group of clinically and genetically overlapping disorders whose etiologies lie in defective cilia. These are antenna-like organelles on the apical surface of numerous cell types in a variety of tissues and organs, the kidney included. Cilia play essential roles during development and tissue homeostasis, and their dysfunction in the kidney has been associated with renal cyst formation and renal failure. Recently, the term “renal ciliopathies” was coined for those human genetic disorders that are characterized by nephronophthisis, cystic kidneys or renal cystic dysplasia. This review focuses on renal ciliopathies from a human genetics perspective. We survey the newest insights with respect to gene identification and genotype–phenotype correlations, and we reflect on candidate ciliopathies. The opportunities and challenges of next-generation sequencing (NGS) for genetic renal research and clinical DNA diagnostics are also reviewed, and we discuss the contribution of NGS to the development of personalized therapy for patients with renal ciliopathies.

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Craniofacial ciliopathies: A new classification for craniofacial disorders

Cited by 63 publications

References 103 publications

Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

Fuz Mutant Mice Reveal Shared Mechanisms between Ciliopathies and FGF-Related Syndromes

Neural crest cell signaling pathways critical to cranial bone development and pathology

Current insights into renal ciliopathies: what can genetics teach us?

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