The Wilson disease gene was cloned independently by two groups and designated as ATP7B [25,26]. The gene consists of 22 exons out of which 21 are expressed in the liver. Exon 22 is expressed in the kidney. The size of the exons ranges from 77 bp to 2355 bp. There is a high level of expression of the gene transcript in the liver and kidney with a lower level in the lung and placenta. One finds a good correlation of the pattern of expression and the observed clinical and biochemical features of the disease.
There are more than 250 mutations reported for Wilson disease . Several mutations in the Wilson disease gene, with small insertion/deletions, non-sense, frameshift, and splice-site mutations have been found. Most common mis-sense mutation in many populations is a change from histidine in position 1069 to glutamine. This mutation is found in about 38% of homozygous Wilson disease patients of North European descent. It occurs in a conserved loop motif (SEHPL) which is adjacent to the conserved phosphorylation motif DKTG. It is not clear what specific function is performed by this motif, but it seems to be necessary for the function of the heavy metal ATPases, as this motif is seen conserved in the Wilson disease, Menkes disease and Cop A copper-transporting ATPases [26,28].
It was found that patients homozygous for the His 1069 Glu mutation has later age of onset as compared to the heterozygous patients, i.e., 20 years versus 15.4 years . This His 1069 Glu mutation was found at high frequency in Mediterranean populations. The data from several studies suggest that the His 1069 Glu mutation is the most common molecular defect in the Wilson disease protein and it probably arose from an ancient mutational event .
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