Fig. 17. Rhodopsin
mutations that cause autosomal dominant retinitis pigmentosa (ADRP) and
related diseases. Currently 104 different mutations in the opsin gene are
thought to cause either night blindness or retinitis pigmentosa. Of these,
89 are nucleotide substitutions causing missense or nonsense changes. Four
of the mutations cause splicing defects in the opsin mRNA. Seven mutations
are small deletions, and one is a small insertion. One each is from a gross
deletion, a gross insertion or duplication, and one is a complex rearrangement.
Some loops have comparatively fewer retinitis pigmentosa mutations; for
example, the third cytosolic loop (positions 231 to 252) has no ADRP mutations
and lacked a consistent structure by X-ray diffraction analysis. This may
suggest that this sequence can vary to a limited extent without causing
disease. All the transmembrane helices contain ADRP mutations, suggesting
that these residues are critical for folding, assembly, retinoid interaction,
and interhelix interactions. (This figure was created by Dr. Markus Preising.
His group has assembled a collection of rhodopsin mutants at http://www.retina-international.com/sci-news/rhomut.htm.
Another site that provides up-to-date information about rhodopsin gene lesions
is at available at http://archive.uwcm.ac.uk/uwcm/mg/ns/1/120347.html.)
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