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Molecular and clinical analysis of Japanese patients with persistent congenital hyperinsulinism: predominance of paternally inherited monoallelic mutations in the KATP channel genes.
MedLine Citation:
PMID:  20943781     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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.
Authors:
Tohru Yorifuji; Rie Kawakita; Shizuyo Nagai; Akinori Sugimine; Hiraku Doi; Anryu Nomura; Michiya Masue; Hironori Nishibori; Akihiko Yoshizawa; Shinya Okamoto; Ryuichiro Doi; Shinji Uemoto; Hironori Nagasaka
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-13
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  96     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E141-5     Citation Subset:  AIM; IM    
Affiliation:
Department of Pediatric Endocrinology and Metabolism, Osaka City General Hospital, Miyakojima, Osaka, Japan. t-yorifuji@hospital.city.osaka.jp
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