Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome

Pediatr Nephrol. 2006 Jan;21(1):32-5. doi: 10.1007/s00467-005-2054-y. Epub 2005 Oct 21.


Joubert syndrome (JBTS) is an autosomal recessive multisystem disease characterized by cerebellar vermis aplasia, mental retardation, muscular hypotonia, an irregular breathing pattern in the neonatal period and abnormal eye movements. Some individuals have progressive renal failure characterized by nephronophthisis (NPHP) and/or retinal dystrophy. Homozygous deletions of NPHP1 on chromosome 2q13 have been identified in individuals with NPHP-associated JBTS. Recently, mutations in AHI1 on chromosome 6q23.3 were found in JBTS patients without NPHP. Here, by direct sequencing, we identify novel truncating mutations within AHI1 in affected patients from two families. One patient had the association of JBTS and NPHP with chronic renal failure. This is the first report of AHI1 mutations causing JBTS associated with NPHP, confirming the clinical and genetic heterogeneity of NPHP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Vesicular Transport
  • Adolescent
  • Adult
  • Apnea / genetics
  • Ataxia / genetics
  • Cerebellum / abnormalities*
  • Child
  • DNA Mutational Analysis
  • Humans
  • Intellectual Disability / genetics
  • Kidney Diseases / genetics*
  • Male
  • Muscle Hypotonia / genetics
  • Mutation*
  • Ocular Motility Disorders / genetics
  • Syndrome


  • AHI1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport