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. 1985 Jul;76(1):378–380. doi: 10.1172/JCI111973

Posttranslational cleavage of proinsulin is blocked by a point mutation in familial hyperproinsulinemia.

Y Shibasaki, T Kawakami, Y Kanazawa, Y Akanuma, F Takaku
PMCID: PMC423787  PMID: 4019786

Abstract

Familial hyperproinsulinemia is characterized by the accumulation of proinsulin-like material (PLM) in the plasma of affected patients. This disorder is inherited in an autosomal dominant fashion. The accumulation of PLM is thought to be due to the impaired conversion of proinsulin to insulin. Although PLM has been suggested to have an amino acid substitution, it has been impossible to locate and identify a substituted amino acid, due to the difficulty in isolating sufficient amounts of PLM from plasma samples. Therefore, we analyzed leukocyte DNA from one member of a proinsulinemic family, and we found a point mutation that changed guanine to adenine in the insulin gene. This transition implies that a substitution of histidine for arginine has occurred at amino acid position 65. Furthermore, it indicates that arginine at 65 is essential for the conversion of proinsulin to insulin. Our results suggest a novel mechanism by which disease can be incurred: a heritable disorder can result from a posttranslational processing abnormality caused by a point mutation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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