C. Desboismouthon et al., LIPOATROPHIC DIABETES - GENETIC EXCLUSION OF THE INSULIN-RECEPTOR GENE, The Journal of clinical endocrinology and metabolism, 80(1), 1995, pp. 314-319
Lipoatrophic diabetes (LD) is a syndrome with congenital or delayed on
set, characterized by severe insulin resistance and generalized lipoat
rophy. Using denaturing gradient gel electrophoresis and sequencing, w
e have investigated the contribution of defects in the insulin recepto
r (IR) gene in LD. First, we performed an association study between th
e LR gene and congenital Lipoatrophy in two families with consanguineo
us parents and one or two affected children (patients D-1, D-2, and D-
3). Segregation analysis of intragenic polymorphisms excluded a linkag
e between the IR locus and the LD phenotype in both families. Second,
are screened for mutations in all exons and splice site junctions of t
he IR gene from patients D-1-D-3 and 11 additional unrelated patients
with congenital or delayed forms of LD. The IR sequence proved to be n
ormal in all 14 subjects because nucleotide variations that we detecte
d were silent. The relative levels of expression of the 2 alleles of t
he IR gene were evaluated by allele-specific oligonucleotide hybridiza
tion in cells from most of these patients, and no gross alteration was
detected. Overall, these results provide the first clear evidence aga
inst the involvement of the IR gene in the pathogenesis of any clinica
l form of LD.