Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus

D Mackay, AM Coupe, J Shield, J Storr, I Temple… - Human genetics, 2002 - Springer
D Mackay, AM Coupe, J Shield, J Storr, I Temple, D Robinson
Human genetics, 2002Springer
Transient neonatal diabetes mellitus (TNDM) is a rare disease believed to result from
overexpression of a paternally expressed gene controlled by a differentially methylated CpG
island on chromosome 6q24. Two genes partially overlap the island: the cell-cycle-control
gene ZAC and the untranslated gene HYMAI, the function of which is currently unknown.
Proof that either gene is involved in TNDM would require demonstration that imprinted
expression is relaxed in TNDM patients; this has hitherto been lacking because of the rarity …
Abstract
Transient neonatal diabetes mellitus (TNDM) is a rare disease believed to result from overexpression of a paternally expressed gene controlled by a differentially methylated CpG island on chromosome 6q24. Two genes partially overlap the island: the cell-cycle-control gene ZAC and the untranslated gene HYMAI, the function of which is currently unknown. Proof that either gene is involved in TNDM would require demonstration that imprinted expression is relaxed in TNDM patients; this has hitherto been lacking because of the rarity of the disease and the lack of imprinted expression in the lymphoblastoid cells that are generally the only resource available for study. Here, we show, for the first time, the aberrant expression of imprinted genes in a TNDM patient. In TNDM fibroblasts, the monoallelic expression of both ZAC and HYMAI is relaxed, providing strong supportive evidence that the presence of two unmethylated alleles of this locus is indeed associated with the inappropriate gene expression of neighbouring genes.
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