Evaluation of the TUB Gene in Patients with Retinitis Pigmentosa

Abstract

Abstract: : Purpose: TUB is the first identified member of the TULP family of proteins with unknown function. A spontaneous mutation in murine tub causes retinal degeneration, obesity, and deafness. Mutations in another member of the TULP family, TULP1, are a cause of autosomal recessive retinitis pigmentosa (RP). These findings prompted us to investigate TUB as a candidate gene for RP. Methods: To date, a complete screen (all 13 exons) for mutations in 95 unrelated patients with isolate RP and a partial screen (4 of 13 exons) for mutations in 95 unrelated patients with autosomal recessive RP have been performed using exon-by-exon SSCP. Variant bands were further analyzed by direct genomic sequencing. Results: Three missense sequence changes (Lys363Arg, Arg419Gly, and Val431Ile) and four isocoding changes (Glu65Glu, Lys81Lys, Gly175Gly, and Ser415Ser) were found in patients with isolate RP. All three missense changes affect residues in the highly conserved C-terminal region of the protein. The Lys363Arg missense change was found heterozygously in 7 patients and the Arg419Gly and Val431Ile changes were each identified heterozygously in 1 patient. Cosegregation analysis in the respective families is pending to help determine whether the three observed missense sequence anomalies are pathogenic. In addition, three variant bands have been identified in three different exons. Sequence analysis of the DNA corresponding to these variants is ongoing. Conclusion: We report seven sequence changes in the coding region of TUB in patients with RP. The possible pathogenic role of these changes is currently under investigation. We are proceeding with an evaluation of the remaining exons in the 95 recessive RP patients and an evaluation of all exons in additional patients with allied diseases.

Keywords: 335 candidate gene analysis • 562 retinal degenerations: hereditary • 480 mutations