Mutations in GRIP1 Cause Fraser Syndrome

Maartje J. Vogel, Patrick van Zon, Louise Brueton, Marleen Gijzen, Marc van Tuil, Philip Cox, Denny Schanze, Ariana Kariminejad, Siavash Ghaderi-Sohi, Edward Blair, Martin Zenker, Peter J. Scambler, Hans Kristian Ploos van Amstel, MM van Haelst

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Fraser syndrome (FS) is a autosomal recessive malformation syndrome characterised by cryptophthalmos, syndactyly and urogenital defects. FS is a genetically heterogeneous condition. Thus far, mutations in FRAS1 and FREM2 have been identified as cause of FS. Both FRAS1 and FREM2 encode extracellular matrix proteins that are essential for the adhesion between epidermal basement membrane and the underlying dermal connective tissues during embryonic development. Mutations in murine Grip1, which encodes a scaffolding protein that interacts with Fras1/Frem proteins, result in FS-like defects in mice.

Objective: To test GRIP1 for genetic variants in FS families that do not have mutations in FRAS1 and FREM2.

Methods and results: In three unrelated families with parental consanguinity, GRIP1 mutations were found to segregate with the disease in an autosomal recessive manner (donor splice site mutation NM_021150.3:c.2113+1G→C in two families and a 4-bp deletion, NM_021150.3:c.1181_1184del in the third). RT-PCR analysis of the GRIP1 mRNA showed that the c.2113+1G→C splice mutation causes skipping of exon 17, leading to a frame shift and a premature stop of translation.

Conclusion: Mutations in GRIP1 cause classic FS in humans.
Original languageEnglish
Article number10.1136/jmedgenet-2011-100590
Pages (from-to)303-6
JournalJournal of Medical Genetics
Publication statusPublished - May 2012

Cite this

Vogel, M. J., van Zon, P., Brueton, L., Gijzen, M., van Tuil, M., Cox, P., ... van Haelst, MM. (2012). Mutations in GRIP1 Cause Fraser Syndrome. Journal of Medical Genetics, 303-6. [10.1136/jmedgenet-2011-100590].