title: Mutations in GRIP1 cause Fraser syndrome.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Mutations in GRIP1 cause classic FS in humans.
authors.affiliation: Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands. m.j.vogel@umcutrecht.nl
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Vogel
authors.forename: Patrick
authors.initials: P
authors.lastname: van Zon
authors.forename: Louise
authors.initials: L
authors.lastname: Brueton
authors.forename: Marleen
authors.initials: M
authors.lastname: Gijzen
authors.forename: Marc C
authors.initials: MC
authors.lastname: van Tuil
authors.forename: Phillip
authors.initials: P
authors.lastname: Cox
authors.forename: Denny
authors.initials: D
authors.lastname: Schanze
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.forename: Siavash
authors.initials: S
authors.lastname: Ghaderi-Sohi
authors.forename: Edward
authors.initials: E
authors.lastname: Blair
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scambler
authors.forename: Hans Kristian
authors.initials: HK
authors.lastname: Ploos van Amstel
authors.forename: Mieke M
authors.initials: MM
authors.lastname: van Haelst
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D005333:Fetus / Q000473:pathology; D016368:Frameshift Mutation; D058497:Fraser Syndrome / Q000235:genetics* / Q000473:pathology; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy
chemical_list: D002352:Carrier Proteins; C491310:GRIP1 protein, human; D009419:Nerve Tissue Proteins