Mutations in CSPP1 lead to classical joubert syndrome

Naiara Akizu, Jennifer L. Silhavy, Rasim Ozgur Rosti, Eric Scott, Ali G. Fenstermaker, Jana Schroth, Maha S. Zaki, Henry Sanchez, Neerja Gupta, Madhulika Kabra, Majdi Kara, Tawfeg Ben-Omran, Basak Rosti, Alicia Guemez-Gamboa, Emily Spencer, Roger Pan, Na Cai, Mostafa Abdellateef, Stacey Gabriel, Jan HalbritterFriedhelm Hildebrandt, Hans Van Bokhoven, Murat Gunel, Joseph G. Gleeson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Joubert 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.

Original languageEnglish (US)
Pages (from-to)80-86
Number of pages7
JournalAmerican journal of human genetics
Issue number1
StatePublished - Jan 2 2014

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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