Mutation identification in A 5-generation pedigree with autosomal dominant retinitis pigmentosa

Abstract

An extended 5-generation family has been investigated in which 32 of the 111 family members were diagnosed as having retinitis pigmentosa (RP). The proband was a 58-year old male in whom night-blindness was first observed in early childhood, with almost loss of vision by 52 years of age. The symptoms observed in other family members included night-blindness, impaired vision and visual field loss. Dementia, digital abnormalities, deaf-mutism and mental retardation were variously diagnosed in a number of individuals with RP. The affected and unaffected family members were tested for mutations in a range of candidate genes. The 8 exons of three candidate genes have been analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing techniques. A novel mutation was identified in the rhodopsin gene at codon 52 of exon 1 (TTC-TAC) that resulted in a substitution of Phe to Tyr.

Keywords

autosomal dominant retinitis pigmentosa / rhodopsin gene / mutation identification

References

[1] Pagon R A, Daiger S P. 2000. Retinitis pigmentosa overview. http://www.geneticclinics. org/profiles/rpoverview/details.html

[2] HuD N. Genetic aspects of retinitis pigmentosa in China. Am J Med Genet, 1982, 12: 51-51

[3] Van SoestS, WesterveldA, De JongP T V M, et al.. Retinitis pigmentosa: defined from a molecular point of view. Surv Ophthalmol, 1999, 43: 321-321

[4] McGuireR E, SullivanL S, BlantonS H, et al.. X-linked dominant cone-rod degeneration: linkage mapping of a new locus for retinitis pigmentosa (RP15) to Xp22. 13-p22.11. Am J Hum Genet, 1995, 57: 87-87

[5] MarcosI, RuizA, BlaschakC J, et al.. Mutation analysis of GABRR1 and GABRR2 in autosomal recessive retinitis pigmentosa (RP25). J Med Genet, 2000, 37: e5-e5

[6] BessantA A R, PayneA M, SnowB, et al.. Importance of the autosomal recessive pigmentosa locus on 1q31-q32.1 (RP12) and mutation analysis of the candidate gene RGS16 (RGS-r). J Med Genet, 2000, 37: 384-384

[7] DryjaT P, HahnL B, KajiwaaraK, et al.. Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa. Invest Ophthalmol Vis Sci, 1997, 38: 1972-1972

[8] ManserghF C, Millington-WardS, KennanA, et al.. Retinitis pigmentosa and progressive sensorineural hearing loss caused by a C12258A mutation in the mitochondrial MTTS2 gene. Am J Hum Genet, 1999, 64: 971-971

[9] RostB. Predic Protein. Methods Enzymol, 1996, 266: 525-525

[10] SanderC, SchneiderR. Database of homology-derived structures and the structural meaning of sequence alignment. Proteins, 1991, 9: 56-56

[11] CottonR G H, ScriverC R. Proof of “Disease causing” mutation. Human Mutation, 1998, 12: 1-1

[12] MurakaMi Y. Detection of DNA aberrations in human cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. Tohoku J Exp Med, 1992, 168(2): 247-53