Scientific Publications

Mutations in CSPP1 Lead to Classical Joubert Syndrome.

Publication TypeJournal Article
AuthorsAkizu, N., Silhavy JL, Rosti RO, Scott E., Fenstermaker AG, Schroth J., Zaki MS, Sanchez H., Gupta N., Kabra M., Kara M., Ben-Omran T., Rosti B., Guemez-Gamboa A., Spencer E., Pan R., Cai N., Abdellateef M., Gabriel S., Halbritter J., Hildebrandt F., van Bokhoven H., Gunel M., and Gleeson JG
AbstractJoubert syndrome and related disorders (JSRDs) are genetically heterogeneous and characterized by a distinctive mid-hindbrain malformation. Causative mutations lead to primary cilia dysfunction, which often results in variable involvement of other organs such as the liver, retina, and kidney. We identified predicted null mutations in CSPP1 in six individuals affected by classical JSRDs. CSPP1 encodes a protein localized to centrosomes and spindle poles, as well as to the primary cilium. Despite the known interaction between CSPP1 and nephronophthisis-associated proteins, none of the affected individuals in our cohort presented with kidney disease, and further, screening of a large cohort of individuals with nephronophthisis demonstrated no mutations. CSPP1 is broadly expressed in neural tissue, and its encoded protein localizes to the primary cilium in an in vitro model of human neurogenesis. Here, we show abrogated protein levels and ciliogenesis in affected fibroblasts. Our data thus suggest that CSPP1 is involved in neural-specific functions of primary cilia.
Year of Publication2014
JournalAmerican journal of human genetics
Volume94
Issue1
Pages80-6
Date Published (YYYY/MM/DD)2014/01/02
ISSN Number0002-9297
DOI10.1016/j.ajhg.2013.11.015
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24360807?dopt=Abstract