Identification of a homozygous nonsense mutation in KIAA0556 in a consanguineous family displaying Joubert syndrome

Hum Genet. 2016 Aug;135(8):919-921. doi: 10.1007/s00439-016-1689-z. Epub 2016 May 31.

Abstract

Joubert Syndrome (JS) is an inherited ciliopathy associated with mutations in genes essential in primary cilium function. Whole exome sequencing in a multiplex consanguineous family from India revealed a KIAA0556 homozygous single base pair deletion mutation (c.4420del; p.Met1474Cysfs*11). Knockdown of the gene in zebrafish resulted in a ciliopathy phenotype, rescued by co-injection of wildtype cDNA. Affected siblings present a mild and classical form of Joubert syndrome allowing for further delineation of the JS associated genotypic spectrum.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Adult
  • Animals
  • Cerebellum / abnormalities*
  • Cerebellum / physiopathology
  • Child
  • Child, Preschool
  • Cilia / drug effects
  • Cilia / pathology
  • Ciliopathies / genetics*
  • Ciliopathies / physiopathology
  • Codon, Nonsense / genetics*
  • DNA, Complementary / administration & dosage
  • Disease Models, Animal
  • Exome / genetics
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / physiopathology
  • Female
  • Gene Knockdown Techniques
  • Homozygote
  • Humans
  • Kidney Diseases, Cystic / genetics*
  • Kidney Diseases, Cystic / physiopathology
  • Male
  • Microtubule-Associated Proteins / genetics*
  • Pedigree
  • Phenotype
  • Retina / abnormalities*
  • Retina / physiopathology
  • Zebrafish / genetics

Substances

  • Codon, Nonsense
  • DNA, Complementary
  • KATNIP protein, human
  • Microtubule-Associated Proteins

Supplementary concepts

  • Agenesis of Cerebellar Vermis