ABCC8 p.Arg998*
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[hide] Molecular and clinical analysis of Japanese patien... J Clin Endocrinol Metab. 2011 Jan;96(1):E141-5. Epub 2010 Oct 13. Yorifuji T, Kawakita R, Nagai S, Sugimine A, Doi H, Nomura A, Masue M, Nishibori H, Yoshizawa A, Okamoto S, Doi R, Uemoto S, Nagasaka H
Molecular and clinical analysis of Japanese patients with persistent congenital hyperinsulinism: predominance of paternally inherited monoallelic mutations in the KATP channel genes.
J Clin Endocrinol Metab. 2011 Jan;96(1):E141-5. Epub 2010 Oct 13., [PMID:20943781]
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BACKGROUND: Preoperative identification of the focal form of congenital hyperinsulinism is important for avoiding unnecessary subtotal pancreatectomy. However, neither the incidence nor the histological spectrum of the disease is known for Japanese patients. AIMS: The aim of the study was to elucidate the molecular and histological spectrum of congenital hyperinsulinism in Japan. SUBJECTS: Thirty-six Japanese infants with persistent congenital hyperinsulinism were included in the study. METHODS: All exons of the ATP-sensitive potassium channel (K(ATP) channel) genes (KCNJ11 and ABCC8), the GCK gene, and exons 6 and 7 and 10-12 of the GLUD1 gene were amplified from genomic DNA and directly sequenced. In patients with K(ATP) channel mutations, the parental origin of each mutation was determined, and the results were compared with the histological findings of surgically treated patients. In one of the patients with scattered lesions, islets were sampled by laser capture microdissection for mutational analysis. RESULTS: Mutations were identified in 24 patients (66.7%): five in GLUD1 and 19 in the K(ATP) channel genes. Sixteen had a paternally derived, monoallelic K(ATP) channel mutation predictive of the focal form. In 10 patients who underwent pancreatectomy, the molecular diagnosis correctly predicted the histology, more accurately than [18F]-3,4-dihydroxyphenylalanine positron emission tomography scans. Three patients showed focal lesions that occupied larger areas of the pancreas. Preferential loss of the maternal allele was observed in these islets. CONCLUSION: The majority of the Japanese patients with K(ATP) channel hyperinsulinism (84.2%) demonstrated paternally inherited monoallelic mutations that accurately predicted the presence of the focal form.
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No. Sentence Comment
50 p.R836X and p.R998X in ABCC8 were identified in five and three unrelated patients, respectively, possibly representing relatively common mutations in Japanese.
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ABCC8 p.Arg998* 20943781:50:14
status: NEW76 Parental origin 1 F 9 months 38 ͓2.1͔ 4.8 ͓33͔ 83 ͓49͔ GLUD1 c.661CϾT p.R221C yes ND F, D 2 M 7 months 30 ͓1.7͔ 3 ͓21͔ 132 ͓77͔ GLUD1 c.797AϾG p.Y266C yes ND F, D 3 F 3 months 29 ͓1.6͔ 4 ͓28͔ 246 ͓144͔ GLUD1 c.1336GϾA p.G446S Yes ND F, D 4 M 10 months Ͻ45 ͓2.5͔ 7.7 ͓53͔ 154 ͓90͔ GLUD1 c.1229AϾG p.N410S No ND F, D 5 M 0 d 10 ͓0.6͔ 10 ͓69͔ 250 ͓147͔ GLUD1 c.1229AϾC p.N410T Yes ND F, D 6a F 2 d 31 ͓1.7͔ 30.2 ͓210͔ 78 ͓46͔ ABCC8 c.382GϾA c.3748CϾT p.E128K p.R1250X Yes, Yes Biparental 7 M 2 d 5 ͓0.3͔ 7.5 ͓52͔ 131 ͓77͔ ABCC8 c.2506CϾT c.4575_4587del13 p.R836X p.M1524Mfs1539X Yes, No Biparental F, O 8 M 0 d Ͻ45 ͓2.5͔ 11 ͓76͔ 58 ͓34͔ ABCC8 c.4516GϾA p.E1506K Yes Mat F, D 9a F 1 month Ͻ20 ͓1.1͔ 42.4 ͓294͔ NA ABCC8 c.2506CϾT p.R836X Yes Pat 10a M 2 d 10 ͓0.56͔ 23.5 ͓163͔ NA ABCC8 c.4412-13GϾA - Yes Pat 11a F 0 d 33 ͓1.8͔ 46.6 ͓324͔ 79 ͓46͔ ABCC8 c.3745GϾT p.V1249F No Pat 12a F 3 months 20 ͓1.1͔ 5.16 ͓36͔ 78 ͓46͔ ABCC8 c.2992CϾT p.R998X Yes Pat 13a F 0 d 23 ͓1.3͔ 101 ͓701͔ 45 ͓24͔ ABCC8 c.4608 ϩ 1GϾA - No Pat 14a M 0 d 22 ͓1.2͔ 22.7 ͓158͔ 75 ͓44͔ ABCC8 c.2992CϾT p.R998X Yes Pat 15a M 5 months 33 ͓1.8͔ 5.42 ͓38͔ NA ABCC8 c.2992CϾT p.R998X Yes Pat 16a M 0 d 28 ͓1.6͔ 38.7 ͓269͔ 66 ͓39͔ ABCC8 c.331GϾA p.G111R Yes Pat 17 F 2 months 15 ͓0.8͔ 9.9 ͓69͔ 90 ͓53͔ ABCC8 c.61_62insG p.V21Gfs88X No Pat F, O 18 M 0 d 19.6 ͓1.1͔ 44 ͓306͔ 79 ͓46͔ ABCC8 c.2506CϾT p.R836X Yes Pat F, O 19 F 7 months 35 ͓1.9͔ 11.2 ͓78͔ 97 ͓57͔ ABCC8 c.2506CϾT p.R836X Yes Pat F, O 20 M 4 months Ͻ45 ͓2.5͔ 7.5 ͓52͔ 84 ͓49͔ ABCC8 c.3928_3929insG p.A1310Gfs1405X No Pat F, O 21 M 2 d 38 ͓2.1͔ 3.4 ͓24͔ 91 ͓53͔ ABCC8 c.4186GϾT p.D1396Y No Pat F 22 F 0 d 9 ͓0.5͔ 22 ͓153͔ NA ABCC8 c.2506CϾT p.R836X Yes Pat F, O 23 M 2 d 0 ͓0͔ 17.3 ͓120͔ 317 ͓186͔ ABCC8 c.4412-13GϾA - Yes Pat F, D 24a M 0 d 33 ͓1.8͔ 21.9 ͓152͔ 75 ͓44͔ KCNJ11 c.637GϾA p.A213T No Pat The clinical data are those at the initial presentation.
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ABCC8 p.Arg998* 20943781:76:1438
status: NEW