[HTML][HTML] Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa

M Martínez-Gimeno, MJ Gamundi… - … & visual science, 2003 - arvojournals.org
M Martínez-Gimeno, MJ Gamundi, I Hernan, M Maseras, E Millá, C Ayuso
Investigative ophthalmology & visual science, 2003arvojournals.org
purpose. Mutations in the systemically expressed pre-mRNA splicing-factor genes PRPF3,
PRPF8, and PRPF31 have recently been associated with autosomal dominant retinitis
pigmentosa (adRP). This study was intended to identify mutations in PRPF3, PRPF8, and
PRPF31 in 150 Spanish families affected by adRP, to measure the contribution of mutations
in these genes to adRP in that population, and to correlate RP phenotype expression with
mutations in pre-mRNA splicing-factor genes. methods. Denaturing gradient gel …
Abstract
purpose. Mutations in the systemically expressed pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 have recently been associated with autosomal dominant retinitis pigmentosa (adRP). This study was intended to identify mutations in PRPF3, PRPF8, and PRPF31 in 150 Spanish families affected by adRP, to measure the contribution of mutations in these genes to adRP in that population, and to correlate RP phenotype expression with mutations in pre-mRNA splicing-factor genes.
methods. Denaturing gradient gel electrophoresis (DGGE) and direct genomic sequencing were used to evaluate the complete coding region and flanking intronic sequences of the PRPF31 gene, exon 42 of PRPF8, and exon 11 of PRPF3 for mutations in 150 unrelated index patients with adRP. Ophthalmic and electrophysiological examination of patients with RP and their relatives was performed according to preexisting protocols.
results. Three nonsense mutations caused by insertion and deletion sequences and two missense mutations (Arg2310Gly) and within the stop codon of the PRPF8 gene (TGA→ TTG), were detected in five unrelated heterozygous patients. Three patients were heterozygous carriers of different nonsense mutations in exon 8 of the PRPF31, gene and one Thr494Met mutation was found in exon 11 of the PRPF3 gene. Cosegregation of the mutation in PRPF8 and PRPF3 with adRP was observed. However, two nonsense mutations in PRPF31 causing adRP detected in two families showed asymptomatic carriers.
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