To the best of our knowledge, CHI due to homozygous ABCC8
mutations and evolution to complete insulin deficient-diabetes later in life has not been reported.
Los genes mas afectados son: KCNJ11, ABCC8
, GCK, SLC2A2, HNF1A, HNFqB, PDX1, PAX4, WFS1 y PPARG.
Yapilan calismalarda diyabetin kromozom 6q24 anormallikleri ve glikolitik enzimler, glukokinaz ve pankreatik P-hucresi ATP-duyarli potasyum kanalinin (KATP) iki protein alt birimini (Kir6.2 ve SUR1) kodlayan genlerde (KCNJ11 ve ABCC8
) mutasyonlardan kaynaklanabilecegi gosterilmistir.
 Human genes: KCNJ11, potassium inwardly-rectifying channel, subfamily J, member 11; ABCC8
, ATP-binding cassette, sub-family C (CFTR/MRP), member 8; SLC30A8, solute carrier family 30 (zinc transporter), member 8.
Mutations in the genes ABCC8
and KCNJ11 coding SUR1 and [K.sub.IR]6.2 respectively have been reported to cause familial hyperinsulinaemia of infancy (HI) (22).
Herein, we report two cases of diazoxide and octreotide unresponsive CHI, due to homozygous ABCC8
gene mutations in which sirolimus had to be discontinued because of drug related hepatotoxicity.
Kahn et al., "Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8
A1369S influence progression to diabetes and response to interventions in the diabetes prevention program," Diabetes, vol.
Cave et al., "Activating mutations in the ABCC8
gene in neonatal diabetes mellitus," New England Journal of Medicine, vol.
Although mutations are present in KCNJ11, ABCC8
and INS genes in approximately half of the cases with neonatal diabetes, the cause is still not known in about 30% (1-3).
As a second example in which variants of a diabetes-associated gene maybe linked to the efficacy of specific drugs, a single published report has shown a significant correlation of polymorphisms of the ATP-binding cassette, subfamily C (CFTR/MRP), member 8 (ABCC8
), gene with sulfonylurea responsiveness in type 2 diabetes (33).
PNDM is a genetically heterogeneous disorder due to mutations in 23 different genes described to date: KCNJ11, ABCC8
, FOXP3, GCK, PDX1, pancreas-specific transcription factor 1A (PTF1A), EIF2AK3, SLC2A2, GATA6, GATA4, SLC19A2, WFS1, NEUROD1, NEUROG3, RFX6, LRBA, NKX2-2, MNX1, IER3IP1, INS, S T A T 3 , GLIS3 and HNF1B (3,4,5,6,7,8,9).
Owen et al., "Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8
) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes," Diabetes, vol.