Mutational analysis of the RPGRIP1L gene in patients with Joubert syndrome and nephronophthisis

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 ge...

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Bibliographic Details
Published in:Kidney international 2007-12, Vol.72 (12), p.1520-1526
Main Authors: Wolf, M.T.F., Saunier, S., O'Toole, J.F., Wanner, N., Groshong, T., Attanasio, M., Salomon, R., Stallmach, T., Sayer, J.A., Waldherr, R., Griebel, M., Oh, J., Neuhaus, T.J., Josefiak, U., Antignac, C., Otto, E.A., Hildebrandt, F.
Format: Article
Language:English
Subjects:
Adult
Cerebellar Diseases - genetics
Child
DNA Mutational Analysis
Eye Diseases - genetics
Family Health
Female
Genetic Linkage
Humans
Joubert syndrome
Kidney Diseases, Cystic - genetics
Male
nephronophthisis
Pedigree
Point Mutation
Proteins - genetics
RPGRIP1L
Syndrome
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Summary: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.
ISSN:0085-2538
1523-1755
DOI:10.1038/sj.ki.5002630