title: Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome.
abstract: 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.
authors.affiliation: Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Utsch
authors.forename: John A
authors.initials: JA
authors.lastname: Sayer
authors.forename: Massimo
authors.initials: M
authors.lastname: Attanasio
authors.forename: Rob Rodrigues
authors.initials: RR
authors.lastname: Pereira
authors.forename: Michael
authors.initials: M
authors.lastname: Eccles
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Otto
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D033942:Adaptor Proteins, Vesicular Transport; D000293:Adolescent; D000328:Adult; D001049:Apnea / Q000235:genetics; D001259:Ataxia / Q000235:genetics; D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics; D009154:Mutation; D015835:Ocular Motility Disorders / Q000235:genetics; D013577:Syndrome
chemical_list: C487178:AHI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport