Novel OFD1 frameshift mutation in a Chinese boy with Joubert syndrome: a case report and literature review

Clin Dysmorphol. 2017 Jul;26(3):135-141. doi: 10.1097/MCD.0000000000000183.


Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of ciliopathy with a key diagnostic feature of 'molar tooth sign' in brain MRI. So far, over 20 causative genes have been identified, but only one gene (OFD1) results in X-linked Joubert syndrome 10 (JBTS10). Six mutations in the OFD1 gene have been found to cause JBTS10. In this study, we identified a novel OFD1 mutation of c.2843_2844 delAA (p.Lys948ArgfsX) in a 3-month-old boy with a 'molar tooth sign' and clinical features of JBTS using targeted exome next-generation sequencing. The de-novo OFD1 mutation in exon 21 leads to a frameshift mutation generating a prematurely truncated protein and is predicted to partly reduce the function of the OFD1 protein. Our study expands the genotype-phenotype spectrum in JBTS and will have applications in prenatal and early diagnosis of the disorder. This is the first report of the OFD1 mutation causing JBTS in a Chinese population.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics
  • Cerebellar Diseases / genetics*
  • Cerebellum / abnormalities
  • China
  • Exome Sequencing
  • Exons
  • Eye Abnormalities / genetics
  • Frameshift Mutation / genetics
  • Genetic Diseases, X-Linked / genetics*
  • Humans
  • Infant
  • Kidney Diseases, Cystic / genetics
  • Male
  • Muscle Hypotonia / genetics*
  • Mutation
  • Orofaciodigital Syndromes / genetics
  • Proteins / genetics*
  • Proteins / metabolism*
  • Retina / abnormalities
  • Sequence Analysis, DNA


  • OFD1 protein, human
  • Proteins

Supplementary concepts

  • Agenesis of Cerebellar Vermis
  • Joubert Syndrome 10