Journal article
Mutations in CSPP1 cause primary cilia abnormalities and joubert syndrome with or without Jeune asphyxiating thoracic dystrophy
K Tuz, R Bachmann-Gagescu, DR O'Day, K Hua, CR Isabella, IG Phelps, AE Stolarski, BJ O'Roak, JC Dempsey, C Lourenco, A Alswaid, CG Bönnemann, L Medne, S Nampoothiri, Z Stark, RJ Leventer, M Topçu, A Cansu, S Jagadeesh, S Done Show all
American Journal of Human Genetics | Published : 2014
Abstract
Joubert syndrome (JBTS) is a recessive ciliopathy in which a subset of affected individuals also have the skeletal dysplasia Jeune asphyxiating thoracic dystrophy (JATD). Here, we have identified biallelic truncating CSPP1 (centrosome and spindle pole associated protein 1) mutations in 19 JBTS-affected individuals, four of whom also have features of JATD. CSPP1 mutations explain ∼5% of JBTS in our cohort, and despite truncating mutations in all affected individuals, the range of phenotypic severity is broad. Morpholino knockdown of cspp1 in zebrafish caused phenotypes reported in other zebrafish models of JBTS (curved body shape, pronephric cysts, and cerebellar abnormalities) and reduced ci..
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Awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development
Funding Acknowledgements
Our deepest thanks go to all of the individuals with Joubert syndrome and their families. This work was supported in part by the Swiss National Science Foundation (PZ00P3_142404 to R.B.-G.), the March of Dimes Foundation (5-FY09-29 to R.J.F.), and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (R01NS064077 and University of Washington Intellectual and Developmental Disabilities Research Center Genetics Core P30HD002274 to D.D. and R01NS064283 to R.J.F.). We also acknowledge private donations from the families of children with Joubert syndrome.