Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis

Craniosynostosis, the premature fusion of the calvarial bones, has numerous etiologies. Among them, several involve mutations in genes related to the TGFb signaling pathway, a critical molecular mediator of human development. These TGFb pathway-associated craniosynostosis syndromes include Loeys–Die...

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Main Authors: Jonas Gustafson, Maria Bjork, Conny M. A. van Ravenswaaij-Arts, Michael L. Cunningham
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Case Reports in Genetics
Online Access:http://dx.doi.org/10.1155/2022/3239260
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author Jonas Gustafson
Maria Bjork
Conny M. A. van Ravenswaaij-Arts
Michael L. Cunningham
author_facet Jonas Gustafson
Maria Bjork
Conny M. A. van Ravenswaaij-Arts
Michael L. Cunningham
author_sort Jonas Gustafson
collection DOAJ
description Craniosynostosis, the premature fusion of the calvarial bones, has numerous etiologies. Among them, several involve mutations in genes related to the TGFb signaling pathway, a critical molecular mediator of human development. These TGFb pathway-associated craniosynostosis syndromes include Loeys–Dietz syndrome (LDS) and Shprintzen–Goldberg syndrome (SGS). LDS and SGS have many similarities common to fibrillinopathies, specifically Marfan syndrome (MFS), which is caused by mutations in FBN1. Historically discriminating features of MFS from LDS and SGS are (1) the presence of ectopia lentis (the subluxation/dislocation of the ocular lens) and (2) the absence of craniosynostosis. Curiously, several instances of a seemingly novel syndrome involving only craniosynostosis and ectopia lentis have recently been reported to be caused by recessive mutations in ADAMTSL4, a poorly characterized gene as of yet. Here, we report on two new cases of craniosynostosis with ectopia lentis, each harboring recessive mutations in ADAMTSL4. We also discuss a proposed mechanism for the relationship between ADAMTSL4, FBN1, and TGFb pathway-related syndromes.
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spelling doaj-art-d5aaa8b618f342bcaf2d01ac4e626ada2025-08-20T03:19:33ZengWileyCase Reports in Genetics2090-65522022-01-01202210.1155/2022/3239260Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia LentisJonas Gustafson0Maria Bjork1Conny M. A. van Ravenswaaij-Arts2Michael L. Cunningham3Seattle Children’s Research InstituteNärhälsan Ågårdsskogens VårdcentralUniversity of GroningenSeattle Children’s Research InstituteCraniosynostosis, the premature fusion of the calvarial bones, has numerous etiologies. Among them, several involve mutations in genes related to the TGFb signaling pathway, a critical molecular mediator of human development. These TGFb pathway-associated craniosynostosis syndromes include Loeys–Dietz syndrome (LDS) and Shprintzen–Goldberg syndrome (SGS). LDS and SGS have many similarities common to fibrillinopathies, specifically Marfan syndrome (MFS), which is caused by mutations in FBN1. Historically discriminating features of MFS from LDS and SGS are (1) the presence of ectopia lentis (the subluxation/dislocation of the ocular lens) and (2) the absence of craniosynostosis. Curiously, several instances of a seemingly novel syndrome involving only craniosynostosis and ectopia lentis have recently been reported to be caused by recessive mutations in ADAMTSL4, a poorly characterized gene as of yet. Here, we report on two new cases of craniosynostosis with ectopia lentis, each harboring recessive mutations in ADAMTSL4. We also discuss a proposed mechanism for the relationship between ADAMTSL4, FBN1, and TGFb pathway-related syndromes.http://dx.doi.org/10.1155/2022/3239260
spellingShingle Jonas Gustafson
Maria Bjork
Conny M. A. van Ravenswaaij-Arts
Michael L. Cunningham
Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis
Case Reports in Genetics
title Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis
title_full Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis
title_fullStr Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis
title_full_unstemmed Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis
title_short Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis
title_sort mechanism of disease recessive adamtsl4 mutations and craniosynostosis with ectopia lentis
url http://dx.doi.org/10.1155/2022/3239260
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