Two novel mutations in the C-terminal region of centrosomal protein 290 (CEP290) result in classic Joubert syndrome

J Child Neurol. 2015 May;30(6):772-6. doi: 10.1177/0883073814535488. Epub 2014 May 21.

Abstract

Joubert syndrome is a neurologic disorder with a pathognomonic "molar tooth sign" on brain imaging. The purpose of this study was to identify potential mutations in a Chinese patient with Joubert syndrome by targeted massively parallel sequencing. Taking advantage of high-throughput DNA sequencing technologies, 18 Joubert-causing genes of a Chinese patient with classic Joubert syndrome were sequenced at a time, and 2 novel variants in the CEP290 gene (c.7323_7327delAGAAG and c.6012-2A>G) were identified in this patient. Sanger validation showed that 2 variants were inherited from each parents, respectively. Both variants are located in the C-terminal region of the CEP290 protein and are predicted to be deleterious. The results support that the combination of targeted genes enrichment and next-generation sequencing is valuable molecular diagnostic tool and suitable for clinical application.

Keywords: CEP290; Joubert syndrome; compound heterozygosity; next-generation sequencing; novel mutations.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics
  • Antigens, Neoplasm / genetics*
  • Cell Cycle Proteins
  • Cerebellum / abnormalities*
  • Child
  • China
  • Cytoskeletal Proteins
  • Eye Abnormalities / genetics
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Kidney Diseases, Cystic / genetics
  • Male
  • Mutation
  • Neoplasm Proteins / genetics*
  • Retina / abnormalities*

Substances

  • Antigens, Neoplasm
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • Neoplasm Proteins

Supplementary concepts

  • Agenesis of Cerebellar Vermis