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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Molecular scanning of the insulin receptor gene in women with polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is a common disorder characterized by chronic anovulation and infertility, hyperandrogenaemia, and frequently insulin resistance. This study investigated whether mutations in the insulin receptor gene could explain the insulin resistance in subjects with PCOS. From a total of 108 women with PCOS, a subgroup of 24 were selected on the criteria of being in the upper quartile for insulin resistance as assessed by fasting serum insulin, insulin area under the curve following 75 g oral glucose tolerance test, and endogenous glucose disposal as a measure of insulin sensitivity. An additional five normal women were also investigated. The entire coding region of the insulin receptor gene, comprising of 22 exons, was amplified by the PCR using genomic DNA and then subjected to single-stranded conformation polymorphism (SSCP) analysis to screen for single-base DNA sequence changes. DNA sequencing revealed that SSCP variants were detected in regions encompassing exons 3, 6-8, 11, 13, 15, 17, and 22. SSCP variants in regions of exons 3, 6, 7, 11, 15 and 22 were caused by nucleotide substitutions within intronic regions flanking the exon. The considerable variation seen in the 5' intron of exon 3 was found to be caused by variation in the number of (ATTT, 8-11) and (TC, 10-13) short sequence repeats. SSCP variants in exons 8 (Asp519, Ala523), 13 (Asn 838), and 17 (Tyr984, His1058) were caused by known silent polymorphisms. Southern blotting experiments excluded major gene deletions, insertions, or rearrangements. We conclude that insulin resistance in subjects with PCOS is not commonly a consequence of missense or nonsense mutations in the insulin receptor gene.[1]


  1. Molecular scanning of the insulin receptor gene in women with polycystic ovarian syndrome. Talbot, J.A., Bicknell, E.J., Rajkhowa, M., Krook, A., O'Rahilly, S., Clayton, R.N. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
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