Abstract
Objective: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a disorder of glucose metabolism that is characterized by dysregulated secretion of insulin from pancreatic β-cells. This disease has been reported to be associated with mutations of the sulfonylurea receptor SUR1 (ABCC8) or the inward-rectifying potassium channel Kir6.2 (KCNJ11), which are two subunits of the pancreatic β-cell ATP-sensitive potassium channel. Patients and Methods: In 14 Japanese PHHI patients, all exons of SUR1 and Kir6.2 genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Four patients responded to diazoxide, and nine patients underwent a subtotal pancreatectomy. Histologically, seven patients were diagnosed to have a focal form and two a diffuse form of the disease. Results: We found nine novel mutations in the SUR1 gene and two in the Kir6.2 gene. In the SUR1 gene mutations, three were nonsense mutations (Y512X, Y1354X and G1469X), one was a one-base deletion in exon 7, and two were missense mutations in the nucleotide-binding domain 2 (K1385Q, R1487K). The other three mutations occurred in introns 14, 29 and 36, which might cause aberrant splicing of RNA. Two siblings in one family were heterozygotes for a missense mutation, K1385Q, which was maternally inherited. In Kir6.2 gene screening, one patient was found to be a compound heterozygote of a missense mutation (R34H) and a one-base deletion (C344fs/ter). Conclusion: The novel mutations reported here could be pathological candidates for PHHI in Japan. They also reveal that SUR1 and Kir6.2 mutations in the Japanese population exhibit heterogeneity and that they occurred at a frequency similar to other genetic populations.
| Original language | English |
|---|---|
| Pages (from-to) | 458-465 |
| Number of pages | 8 |
| Journal | Clinical Endocrinology |
| Volume | 62 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2005 |
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All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Endocrinology
Cite this
Genotypes of the pancreatic β-cell K-ATP channel and clinical pnenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy. / Ohkubo, Kumiko; Nagashima, Mariko; Naito, Yuko; Taguchi, Tomoaki; Suita, Sachiyo; Okamoto, Nobuhiko; Fujinaga, Hideshi; Tsumura, Kumi; Kikuchi, Kiyoshi; Ono, Junko.
In: Clinical Endocrinology, Vol. 62, No. 4, 01.04.2005, p. 458-465.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Genotypes of the pancreatic β-cell K-ATP channel and clinical pnenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy
AU - Ohkubo, Kumiko
AU - Nagashima, Mariko
AU - Naito, Yuko
AU - Taguchi, Tomoaki
AU - Suita, Sachiyo
AU - Okamoto, Nobuhiko
AU - Fujinaga, Hideshi
AU - Tsumura, Kumi
AU - Kikuchi, Kiyoshi
AU - Ono, Junko
PY - 2005/4/1
Y1 - 2005/4/1
N2 - Objective: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a disorder of glucose metabolism that is characterized by dysregulated secretion of insulin from pancreatic β-cells. This disease has been reported to be associated with mutations of the sulfonylurea receptor SUR1 (ABCC8) or the inward-rectifying potassium channel Kir6.2 (KCNJ11), which are two subunits of the pancreatic β-cell ATP-sensitive potassium channel. Patients and Methods: In 14 Japanese PHHI patients, all exons of SUR1 and Kir6.2 genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Four patients responded to diazoxide, and nine patients underwent a subtotal pancreatectomy. Histologically, seven patients were diagnosed to have a focal form and two a diffuse form of the disease. Results: We found nine novel mutations in the SUR1 gene and two in the Kir6.2 gene. In the SUR1 gene mutations, three were nonsense mutations (Y512X, Y1354X and G1469X), one was a one-base deletion in exon 7, and two were missense mutations in the nucleotide-binding domain 2 (K1385Q, R1487K). The other three mutations occurred in introns 14, 29 and 36, which might cause aberrant splicing of RNA. Two siblings in one family were heterozygotes for a missense mutation, K1385Q, which was maternally inherited. In Kir6.2 gene screening, one patient was found to be a compound heterozygote of a missense mutation (R34H) and a one-base deletion (C344fs/ter). Conclusion: The novel mutations reported here could be pathological candidates for PHHI in Japan. They also reveal that SUR1 and Kir6.2 mutations in the Japanese population exhibit heterogeneity and that they occurred at a frequency similar to other genetic populations.
AB - Objective: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a disorder of glucose metabolism that is characterized by dysregulated secretion of insulin from pancreatic β-cells. This disease has been reported to be associated with mutations of the sulfonylurea receptor SUR1 (ABCC8) or the inward-rectifying potassium channel Kir6.2 (KCNJ11), which are two subunits of the pancreatic β-cell ATP-sensitive potassium channel. Patients and Methods: In 14 Japanese PHHI patients, all exons of SUR1 and Kir6.2 genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Four patients responded to diazoxide, and nine patients underwent a subtotal pancreatectomy. Histologically, seven patients were diagnosed to have a focal form and two a diffuse form of the disease. Results: We found nine novel mutations in the SUR1 gene and two in the Kir6.2 gene. In the SUR1 gene mutations, three were nonsense mutations (Y512X, Y1354X and G1469X), one was a one-base deletion in exon 7, and two were missense mutations in the nucleotide-binding domain 2 (K1385Q, R1487K). The other three mutations occurred in introns 14, 29 and 36, which might cause aberrant splicing of RNA. Two siblings in one family were heterozygotes for a missense mutation, K1385Q, which was maternally inherited. In Kir6.2 gene screening, one patient was found to be a compound heterozygote of a missense mutation (R34H) and a one-base deletion (C344fs/ter). Conclusion: The novel mutations reported here could be pathological candidates for PHHI in Japan. They also reveal that SUR1 and Kir6.2 mutations in the Japanese population exhibit heterogeneity and that they occurred at a frequency similar to other genetic populations.
UR - http://www.scopus.com/inward/record.url?scp=20144389411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144389411&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2265.2005.02242.x
DO - 10.1111/j.1365-2265.2005.02242.x
M3 - Article
C2 - 15807877
AN - SCOPUS:20144389411
VL - 62
SP - 458
EP - 465
JO - Clinical Endocrinology
JF - Clinical Endocrinology
SN - 0300-0664
IS - 4
ER -