Refinement of the 6q chromosomal region implicated in transient neonatal diabetes

Transient neonatal diabetes mellitus (TNDM) is estimated to occur in similar to 1 in 500,000 births and represents 50-60% of cases of neonatal diabetes. The pattern of inheritance of TNDM and its association with chromosome 6 uniparental disomy is consistent with the presence on chromosome 6 of an imprinted gene involved in pancreatic beta-cell development. Systematic screening for chromosome 6 abnormalities in nine families with 13 individuals affected by TNDM revealed paternal isodisomy of chromosome 6 in one child and paternally derived trisomy of the chromosomal region 6q in six children from three unrelated families. To delineate more accurately the region suspected of harboring the gene of interest, precise mapping of the duplicated area was performed in children exhibiting partial 6q trisomy by using microsatellite markers. The smallest region of duplication observed in our patients was flanked by markers D6S308 and D6S1010, which are separated by <1 cM. These findings confirm that TNDM may result from the overexpression of a gene located on chromosome 6q that is exclusively expressed from the paternal allele at least during some periods of life and further refine the localization of this gene.