title: Mutational analysis of the RPGRIP1L gene in patients with Joubert syndrome and nephronophthisis.
abstract: Joubert syndrome (JS) is an autosomal recessive disorder, consisting of mental retardation, cerebellar vermis aplasia, an irregular breathing pattern, and retinal degeneration. Nephronophthisis (NPHP) is found in 17-27% of these patients, which was designated JS type B. Mutations in four separate genes (AHI1, NPHP1, CEP290/NPHP6, and MKS3) are linked to JS. However, missense mutations in a new ciliary gene (RPGRIP1L) were found in type B patients. We analyzed a cohort of 56 patients with JS type B who were negative for mutations in three (AHI1, NPHP1, and CEP290/NPHP6) of the four genes previously linked to the syndrome. The 26 exons encoding RPGRIP1L were analyzed by means of PCR amplification, CEL I endonuclease digestion, and subsequent sequencing. Using this approach, four different mutations in the RPGRIP1L gene in five different families were identified and three were found to be novel mutations. Additionally, we verified that missense mutations are responsible for JS type B and cluster in exon 15 of the RPGRIP1L gene. Our studies confirm that a T615P mutation represents the most common mutation in the RPGRIP1L gene causing disease in about 8-10% of JS type B patients negative for NPHP1, NPHP6, or AHI1 mutations.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109-0646, USA.
authors.forename: M T F
authors.initials: MT
authors.lastname: Wolf
authors.forename: S
authors.initials: S
authors.lastname: Saunier
authors.forename: J F
authors.initials: JF
authors.lastname: O'Toole
authors.forename: N
authors.initials: N
authors.lastname: Wanner
authors.forename: T
authors.initials: T
authors.lastname: Groshong
authors.forename: M
authors.initials: M
authors.lastname: Attanasio
authors.forename: R
authors.initials: R
authors.lastname: Salomon
authors.forename: T
authors.initials: T
authors.lastname: Stallmach
authors.forename: J A
authors.initials: JA
authors.lastname: Sayer
authors.forename: R
authors.initials: R
authors.lastname: Waldherr
authors.forename: M
authors.initials: M
authors.lastname: Griebel
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.forename: T J
authors.initials: TJ
authors.lastname: Neuhaus
authors.forename: U
authors.initials: U
authors.lastname: Josefiak
authors.forename: C
authors.initials: C
authors.lastname: Antignac
authors.forename: E A
authors.initials: EA
authors.lastname: Otto
authors.forename: F
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D000328:Adult; D002526:Cerebellar Diseases / Q000235:genetics*; D002648:Child; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005128:Eye Diseases / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D003598:Cytoskeletal Proteins; D011506:Proteins; C415903:RPGRIP1 protein, human