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Meckel-Gruber syndrome: An update on diagnosis, clinical management, and research advances

Hartill, Verity; Szymanska, Katarzyna; Sharif, Saghira Malik; Wheway, Gabrielle; Johnson, Colin Anfimov

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Verity Hartill

Katarzyna Szymanska

Saghira Malik Sharif

Gabrielle Wheway
Occasional Associate Lecturer - CHSS - DAS

Colin Anfimov Johnson


© 2017 Hartill, Szymanska, Sharif, Wheway and Johnson. Meckel-Gruber syndrome (MKS) is a lethal autosomal recessive congenital anomaly syndrome caused by mutations in genes encoding proteins that are structural or functional components of the primary cilium. Conditions that are caused by mutations in ciliary genes are collectively termed the ciliopathies, and MKS represents the most severe condition in this group of disorders. The primary cilium is a microtubule-based organelle, projecting from the apical surface of vertebrate cells. It acts as an "antenna" that receives and transduces chemosensory and mechanosensory signals, but also regulates diverse signaling pathways, such as Wnt and Shh, that have important roles during embryonic development. Most MKS proteins localize to a distinct ciliary compartment called the transition zone (TZ) that regulates the trafficking of cargo proteins or lipids. In this review, we provide an up-to-date summary of MKS clinical features, molecular genetics, and clinical diagnosis. MKS has a highly variable phenotype, extreme genetic heterogeneity, and displays allelism with other related ciliopathies such as Joubert syndrome, presenting significant challenges to diagnosis. Recent advances in genetic technology, with the widespread use of multi-gene panels for molecular testing, have significantly improved diagnosis, genetic counseling, and the clinical management of MKS families. These include the description of some limited genotype-phenotype correlations. We discuss recent insights into the molecular basis of disease in MKS, since the functions of some of the relevant ciliary proteins have now been determined. A common molecular etiology appears to be disruption of ciliary TZ structure and function, affecting essential developmental signaling and the regulation of secondary messengers.


Hartill, V., Szymanska, K., Sharif, S. M., Wheway, G., & Johnson, C. A. (2017). Meckel-Gruber syndrome: An update on diagnosis, clinical management, and research advances. Frontiers in Pediatrics, 5(244), 1-9.

Journal Article Type Short Survey
Acceptance Date Nov 3, 2017
Publication Date Nov 20, 2017
Deposit Date Nov 21, 2017
Publicly Available Date Nov 21, 2017
Journal Frontiers in Pediatrics
Print ISSN 2296-2360
Electronic ISSN 2296-2360
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 5
Issue 244
Pages 1-9
Keywords Meckel-Gruber syndrome, ciliopathy, cilia, primary cilia, development, developmental disease, genetics
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Additional Information Additional Information : This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.


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