Whole exome sequencing reveals novel CEP104 mutations in a Chinese patient with Joubert syndrome

Mol Genet Genomic Med. 2019 Dec;7(12):e1004. doi: 10.1002/mgg3.1004. Epub 2019 Oct 18.

Abstract

Background: Joubert syndrome (JS, OMIM: 213300) is a recessive developmental disorder characterized by cerebellar vermis hypoplasia and a distinctive mid-hindbrain malformation called the "molar tooth sign" on axial magnetic resonance imaging. To date, more than 35 ciliary genes have been identified as the causative genes of JS.

Methods: Whole exome sequencing was performed to detect the causative gene mutations in a Chinese patient with JS followed by Sanger sequencing. RT-PCR and Sanger sequencing were used to confirm the abnormal transcript of centrosomal protein 104 (CEP104, OMIM: 616690).

Results: We identified two novel heterozygous mutations of CEP104 in the proband, which were c.2364+1G>A and c.414delC (p.Asn138Lysfs*11) (GenBank: NM_014704.3) and consistent with the autosomal recessive inheritance mode.

Conclusion: Our study reported the fourth case of JS patients with CEP104 mutations, which expands the mutation spectrum of CEP104 and elucidates the clinical heterogeneity of JS.

Keywords: CEP104; Joubert syndrome; cerebellar vermis hypoplasia; whole exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Cell Cycle Proteins / genetics*
  • Cerebellum / abnormalities*
  • Child, Preschool
  • Exome Sequencing / methods*
  • Eye Abnormalities / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Kidney Diseases, Cystic / genetics*
  • Male
  • Mutation*
  • Pedigree
  • Retina / abnormalities*
  • Sequence Analysis, DNA

Substances

  • Cell Cycle Proteins
  • Cep104 protein, human

Supplementary concepts

  • Agenesis of Cerebellar Vermis

Associated data

  • GENBANK/NM_014704.3