Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa
- J C Booij1,
- R J Florijn1,
- J B ten Brink1,
- W Loves1,
- F Meire3,
- M J van Schooneveld4,
- P TVM de Jong2,
- A A B Bergen2
- 1Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Ophthalmic Research Institute, Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands
- 2Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Ophthalmic Research Institute, Royal Netherlands Academy of Arts and Sciences, Amsterdam
- 3Department of Ophthalmology, University of Gent, Gent, Belgium
- 4Department of Ophthalmology, University of Utrecht, Utrecht, Netherlands
- Correspondence to: Dr Prof A A B Bergen Department of Ophthalmogenetics, Meibergdreef 47, 1105 BA Amsterdam, Netherlands;
- Received 20 May 2005
- Accepted 18 July 2005
- Revised 13 July 2005
Objective: To identify mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.
Methods: Mutation analysis was carried out in a group of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber’s congenital amaurosis (LCA), or juvenile isolated retinitis pigmentosa (IRP), by denaturing high performance liquid chromatography followed by direct sequencing.
Results: All three groups of patients showed typical combinations of eye signs associated with retinitis pigmentosa: pale optic discs, narrow arterioles, pigmentary changes, and nystagmus. Mutations were found in 34% of patients: in CRB1 (11%), GUCY2D (11%), RPE65 (6%), and RPGRIP1 (6%). Nine mutations are reported, including a new combination of two mutations in CRB1, and new mutations in GUCY2D and RPGRIP1. The new GUCY2D mutation (c.3283delC, p.Pro1069ArgfsX37) is the first pathological sequence change reported in the intracellular C-terminal domain of GUCY2D, and did not lead to the commonly associated LCA, but to a juvenile retinitis pigmentosa phenotype. The polymorphic nature of three previously described (pathological) sequence changes in AIPL1, CRB1, and RPGRIP1 was established. Seven new polymorphic changes, useful for further association studies, were found.
Conclusions: New and previously described sequence changes were detected in retinitis pigmentosa in CRB1, GUCY2D, and RPGRIP1; and in LCA patients in CRB1, GUCY2D, and RPE65. These data, combined with previous reports, suggest that LCA and juvenile ARRP are closely related and belong to a continuous spectrum of juvenile retinitis pigmentosa.
- ARRP, autosomal recessive retinitis pigmentosa
- DHPLC, denaturing high performance liquid chromatography
- IRP, juvenile isolated retinitis pigmentosa
- LCA, Leber’s congenital amaurosis
- RP, retinitis pigmentosa
- autosomal recessive retinitis pigmentosa
- Leber’s congenital amaurosis
- mutation screening
- retinal dystrophy
Competing interests: none declared