American journal of human genetics · 2013
Mutations in CSPP1 lead to classical Joubert syndrome.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Akizu Naiara, Silhavy Jennifer L, Rosti Rasim Ozgur, Scott Eric, Fenstermaker Ali G, Schroth Jana, Zaki Maha S, Sanchez Henry, Gupta Neerja, Kabra Madhulika, Kara Majdi, Ben-Omran Tawfeg, Rosti Basak, Guemez-Gamboa Alicia, Spencer Emily, Pan Roger, Cai Na, Abdellateef Mostafa, Gabriel Stacey, Halbritter Jan, Hildebrandt Friedhelm, van Bokhoven Hans, Gunel Murat, Gleeson Joseph G
Аннотация
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.