CHI within the neonatal period and evolution to diabetes later in life has been reported in individuals with heterozygous inactivating mutations in the hepatocyte nuclear factor 4A and 1A genes (HNF4A and HNF1A) (12,13,14) and dominant mutations in ABCC8
genes in a very limited number of cases (1,7,11,13,15,16,17,18,19,20,21).
In this respect, we examined VHL and ABCC8
, KCNJ11, HNF4A genes in our case, however, no mutation was detected.
Zhang et al., "ABCC8
and ABCC9: ABC transporters that regulate K+ channels," Pflugers Archiv, vol.
Yenidogan diyabetinin yaklasik yarisinda KCNJ11, ABCC8
ve INS genlerinde mutasyonlar olmasina karsin, halen %30 kadarinin nedeni bilinmemektedir (1-3).
Identification of genetic polymorphism in KCNJ11 gene is important in the diagnosis of NDM.11 Mutations in KCNJ11 and ABCC8
genes which encode the Kir6.2 and SUR1 subunits of the pancreatic ATP-sensitive potassium channel respectively have been implicated in the genesis of PNDM.9
Activating mutations in the ABCC8
gene in neonatal diabetes mellitus.
Several inborn errors in the [beta] cell that affect the subunits of the inwardly rectifying potassium channel Kir6.2 [encoded by potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) ] or SUR1 [encoded by ATP-binding cassette, sub-family C (cFTR/MRP), member 8 (ABCC8
)] have been shown to cause neonatal diabetes (11).
Simard's team demonstrated that a gene called ABCC8
starts this overproduction of inflammatory factors and damaging bleeding.
SUR1 and [K.sub.IR]6.2 are located on chromosome 11 (llp15.1) and are encoded by the genes ABCC8
and KCNJ11, respectively (14).
Most cases of CHI are caused by autosomal recessive mutations in the ABCC8
and KCNJ11 genes (1).
Other genes associated with MODY are infrequently detected: HNF1B, IPF, NEUROD, PDX1, KLF11, CEL, PAX4, BLK, ABCC8
and KCNJ11 (3).
Liu et al., "Mutational analysis of ABCC8
, KCNJ11, GLUD1, HNF4A and GCK genes in 30 Chinese patients with congenital hyperinsulinism," Endocrine Journal, vol.
Mutations in the SUR1 (ABCC8
) and the Kir6.2 (KCNJ11) cause familial hyperinsulinemia in infancy , while some polymorphisms in these genes (exon 16-3t/c and exon 18 C/T of ABCC8
and E23K of KCNJ11) have been reported to be associated with T2D in several populations at different degrees [18-23].
Activating mutations of the [K.sub.ATP] channel genes (either potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11), or ATP-binding cassette transporter subfamily C member 8 (ABCC8
)) or insulin gene (INS) are the most common causes of permanent neonatal diabetes mellitus (PNDM), whilst KCNJ11 and ABCC8
mutations have been shown to account for a minority of cases of TNDM [35, 40, 42,43].