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.
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 murineGrip1, 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.
Authors: Nayia Nicolaou; Kirsten Y Renkema; Ernie M H F Bongers; Rachel H Giles; Nine V A M Knoers Journal: Nat Rev Nephrol Date: 2015-08-18 Impact factor: 28.314
Authors: Tyler F Beck; Danielle Veenma; Oleg A Shchelochkov; Zhiyin Yu; Bum Jun Kim; Hitisha P Zaveri; Yolande van Bever; Sunju Choi; Hannie Douben; Terry K Bertin; Pragna I Patel; Brendan Lee; Dick Tibboel; Annelies de Klein; David W Stockton; Monica J Justice; Daryl A Scott Journal: Hum Mol Genet Date: 2012-12-05 Impact factor: 6.150
Authors: Jared Nathanson; Daniel T Swarr; Amihood Singer; Mochi Liu; Amy Chinn; Wendy Jones; Jane Hurst; Nahla Khalek; Elaine Zackai; Anne Slavotinek Journal: Am J Med Genet A Date: 2013-02-08 Impact factor: 2.802
Authors: Valerie K Jordan; Tyler F Beck; Andres Hernandez-Garcia; Peter N Kundert; Bum-Jun Kim; Shalini N Jhangiani; Tomasz Gambin; Molly Starkovich; Jaya Punetha; Ingrid S Paine; Jennifer E Posey; Alexander H Li; Donna Muzny; Chih-Wei Hsu; Amber J Lashua; Xin Sun; Caraciolo J Fernandes; Mary E Dickinson; Kevin P Lally; Richard A Gibbs; Eric Boerwinkle; James R Lupski; Daryl A Scott Journal: Hum Mol Genet Date: 2018-06-15 Impact factor: 6.150