Genomic organization of the human TIMP-1 gene. Investigation of a causative role in the pathogenesis of X-linked retinitis pigmentosa 2.
OBJECTIVE
To evaluate the role of TIMP-1 in inherited retinal degeneration.


METHODS
The genomic structure of the TIMP-1 gene was established and male patients with x-linked retinitis pigmentosa 2 from five families were screened for sequence alterations by direct sequencing in all exons, exon-intron boundaries, and the 5' upstream region of the gene.


RESULTS
TIMP-1 appears to be expressed in the retina at low levels and consists of six exons spanning a genomic region of approximately 4.5 kb on Xp11.23. No disease-specific sequence alterations were identified. A site substitution in exon 5 was observed in samples from control subjects and patients, but it did not alter the amino acid sequence of the protein product.


CONCLUSIONS
The results of this study exclude mutations in the TIMP-1 coding sequence, splice sites, and the 5' upstream region as a cause of retinal degeneration in x-linked retinitis pigmentosa 2. However, an as yet unidentified regulatory element that lies outside these intervals may be implicated. The role of this tightly regulated protein in the normal functioning of the retina has yet to be determined.
Hardcastle
A J
AJ
Department of Molecular Genetics, Institute of Ophthalmology, London, United Kingdom.
Thiselton
D L
DL
Nayudu
M
M
Hampson
R M
RM
Bhattacharya
S S
SS
D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D008040:Genetic Linkage; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D011480:Protease Inhibitors; D012160:Retina / Q000201:enzymology; D012174:Retinitis Pigmentosa / Q000201:enzymology* / Q000209:etiology; D019714:Tissue Inhibitor of Metalloproteinases; D014960:X Chromosome / Q000201:enzymology*
D017931:DNA Primers; D006023:Glycoproteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D004247:DNA