ABCMdb

PMID: 15807877

Ohkubo K, Nagashima M, Naito Y, Taguchi T, Suita S, Okamoto N, Fujinaga H, Tsumura K, Kikuchi K, Ono J
Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy.
Clin Endocrinol (Oxf). 2005 Apr;62(4):458-65., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC8 p.Tyr512* In the SUR1 gene mutations, three were nonsense mutations(Y512X,Y1354XandG1469X),onewasaone-basedeletion in exon 7, and two were missense mutations in the nucleotide-binding domain 2 (K1385Q, R1487K). Login to comment 49 ABCC8 p.Tyr512* ABCC8 p.Gly1469* Exon or intron Nucleotide change Codon Predicted effect Domain Age at onset Birthweight (g) Gestational age (weeks) Therapy Histopathology Long-term outcome Pancreatectomy Diazoxide SUR1 mutation 8 Exon 7 1122delA Q374fs/ter - 1 day 3690 34 - + Sometimes hypoglycaemic 5 Exon 10 C1536A Y512X - 1 day 3635 38 + (80%) - F (tail) N 4 Intron 14 2041-21G → A Aberrant splicing NBD1 1 day 3792 41 + (85%) - F (body) N 6 Intron 29 3653+2T → C Aberrant splicing NBD2 2 months 3470 40 + (80%) - F (tail) N 1 Exon 33 C4062A Y1354X NBD2 1 day 4144 40 + (75-95%) - F (head) N 10 Exon 34 A4153C K1385Q NBD2 1 day 3776 36 - + N 11 Exon 34 A4153C K1385Q NBD2 1 day 4364 38 - + N 12 Exon 36 G4405T G1469X NBD2 3 months 4055 39 + (80%) - F (body) N 2 Intron 36 4415-3G → A Aberrant splicing NBD2 1 day 3803 38 + (80%) - D Insulin-dependent diabetes 13 Exon 37 G4460A R1487K NBD2 1 day 4830 37 + (70%) - F (body) + adenoma N Kir6.2 mutation 14 Exon G101A R34H N terminus 1 day 3104 36 + (95%) - D nd 14 Exon 1032delC C344fs/ter C terminus No mutation 3 2 months 2898 42 + (80%) - F (body) N 7 4 months 3224 40 - + N 9 1 day 2548 39 - + N Nucleotide and codon positions of SUR1 are determined according to the full-length human cDNA sequence incorporating the alternative splice form of exon 17 (GenBank L78207 and L78224). Login to comment 52 ABCC8 p.Tyr512* ABCC8 p.Gly1469* The nucleotide sequence substituted an adenine for a cytosine at nt 1536 (Y512X), and a thymine for a guanine at nt 4405 (G1469X). Login to comment 103 ABCC8 p.Glu1506Lys One is a loss of the serine at codon 1387 (delSer1387),7 while others are missense mutations, R1353H8 and E1506K. Login to comment 104 ABCC8 p.Glu1506Lys 6 The phenotypes in the last mutation are a mild form of congenital hyperinsulinaemic hypoglycaemia in infancy and then gestational or permanent diabetes later.34 The K1385Q mutation may also be inherited autosomal-dominantly and be related to the different phenotypes in insulin secretion in the same manner as E1506K, although the possibility that they are compound heterozygotes of K1385Q with an unknown mutation in either the 5' upstream region or the intronic region of the paternal allele has not yet been ruled out. Login to comment 122 ABCC8 p.Arg1436Gln ABCC8 p.Arg1420Cys To date, only three kinds of SUR1 mutations (I446fsdelT, R1420C and R1436Q) have been reported in Japanese PHHI patients.20,42 We defined 11 novel mutations, and the SUR1 and Kir6.2 mutations account for about 80% of the PHHI cases in this study, although Tanizawa et al.20 reported only about 20% (three kinds of mutations in four patients from the screening of 17 PHHI patients) and Someya et al.42 did not detect any mutations (in eight PHHI patients). Login to comment 130 ABCC8 p.Arg1420Cys ABCC8 p.Phe591Leu For example, the patients having some kinds of missense mutations in the SUR1 gene such as F591L,13 R1420C, 20 R1506K 6 and K1385Q in this report showed mild hypoglycaemia, which is known to be responsive to drug therapy, and thus they do not need an operation. Login to comment