Molecular and Clinical Analysis of Japanese Patients with Persistent Congenital Hyperinsulinism: Predominance of Paternally Inherited Monoallelic Mutations in the KATP Channel Genes
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 elucida...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2011-01, Vol.96 (1), p.E141-E145 |
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| creator | Yorifuji, Tohru Kawakita, Rie Nagai, Shizuyo Sugimine, Akinori Doi, Hiraku Nomura, Anryu Masue, Michiya Nishibori, Hironori Yoshizawa, Akihiko Okamoto, Shinya Doi, Ryuichiro Uemoto, Shinji Nagasaka, Hironori |
| description | 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 (KATP 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 KATP 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 KATP channel genes. Sixteen had a paternally derived, monoallelic KATP 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 KATP channel hyperinsulinism (84.2%) demonstrated paternally inherited monoallelic mutations that accurately predicted the presence of the focal form.
Most of the Japanese patients with congenital KATP-channel hyperinsulinism have the focal form. |
| doi_str_mv | 10.1210/jc.2010-1281 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_822899312</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>822899312</sourcerecordid><originalsourceid>FETCH-LOGICAL-e202t-c8e10505d78ecc93a6d7e8aa519a15315cd8ab6892e5f80a09bd4a43f6a9c5af3</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0EokvLjTPyjV5S_JFsbG6rqF_QVfdQJG7RrDNhvXLsEDtC-8P4fzhquXKyNHrmGet9CfnA2RUXnH0-mivBOCu4UPwVWXFdVkXNdf2arBgTvNC1-HFG3sV4ZIyXZSXfkjPBdClrxVfkzzY4NLODiYLvaOOstwYc3Xhwp2gjDT39CiN4jEh3kCz6FOlvmw50h1MGUh7QJvif6G3Ki3enESfr47yY4vCF7ibswmA9eIOLLUtwynZ3ovf-kNmEHd0GH_IInTV0O6d8J_hIrafpgPTb5mlHmwN4j47eYv7KBXnTg4v4_uU9J99vrp-au-Lh8fa-2TwUKJhIhVHIWcWqrlZojJaw7mpUABXXwCvJK9Mp2K-VFlj1igHT-66EUvZr0KaCXp6TT8_ecQq_ZoypHWw06FzOI8yxVUIorSUXmbz8L8kZr7XiTMiMfnxB5_2AXTtOdoDp1P4rJQPyGUDfBZPDxHHCGNtjmJfgFlm7VN8eTbtU3y7Vy78-MaLk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1017981023</pqid></control><display><type>article</type><title>Molecular and Clinical Analysis of Japanese Patients with Persistent Congenital Hyperinsulinism: Predominance of Paternally Inherited Monoallelic Mutations in the KATP Channel Genes</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Yorifuji, Tohru ; Kawakita, Rie ; Nagai, Shizuyo ; Sugimine, Akinori ; Doi, Hiraku ; Nomura, Anryu ; Masue, Michiya ; Nishibori, Hironori ; Yoshizawa, Akihiko ; Okamoto, Shinya ; Doi, Ryuichiro ; Uemoto, Shinji ; Nagasaka, Hironori</creator><creatorcontrib>Yorifuji, Tohru ; Kawakita, Rie ; Nagai, Shizuyo ; Sugimine, Akinori ; Doi, Hiraku ; Nomura, Anryu ; Masue, Michiya ; Nishibori, Hironori ; Yoshizawa, Akihiko ; Okamoto, Shinya ; Doi, Ryuichiro ; Uemoto, Shinji ; Nagasaka, Hironori</creatorcontrib><description>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 (KATP 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 KATP 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 KATP channel genes. Sixteen had a paternally derived, monoallelic KATP 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 KATP channel hyperinsulinism (84.2%) demonstrated paternally inherited monoallelic mutations that accurately predicted the presence of the focal form.
Most of the Japanese patients with congenital KATP-channel hyperinsulinism have the focal form.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2010-1281</identifier><identifier>PMID: 20943781</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Alleles ; Asian Continental Ancestry Group - genetics ; Congenital Hyperinsulinism - genetics ; Congenital Hyperinsulinism - metabolism ; Congenital Hyperinsulinism - surgery ; DNA ; DNA Mutational Analysis ; Exons ; genomics ; Humans ; Infant ; Infants ; Islets of Langerhans ; KATP Channels - genetics ; KATP Channels - metabolism ; Lasers ; Microdissection ; Mutation ; Nucleotide sequence ; Pancreas ; Pancreatectomy ; Positron emission tomography ; Potassium channels</subject><ispartof>The journal of clinical endocrinology and metabolism, 2011-01, Vol.96 (1), p.E141-E145</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20943781$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yorifuji, Tohru</creatorcontrib><creatorcontrib>Kawakita, Rie</creatorcontrib><creatorcontrib>Nagai, Shizuyo</creatorcontrib><creatorcontrib>Sugimine, Akinori</creatorcontrib><creatorcontrib>Doi, Hiraku</creatorcontrib><creatorcontrib>Nomura, Anryu</creatorcontrib><creatorcontrib>Masue, Michiya</creatorcontrib><creatorcontrib>Nishibori, Hironori</creatorcontrib><creatorcontrib>Yoshizawa, Akihiko</creatorcontrib><creatorcontrib>Okamoto, Shinya</creatorcontrib><creatorcontrib>Doi, Ryuichiro</creatorcontrib><creatorcontrib>Uemoto, Shinji</creatorcontrib><creatorcontrib>Nagasaka, Hironori</creatorcontrib><title>Molecular and Clinical Analysis of Japanese Patients with Persistent Congenital Hyperinsulinism: Predominance of Paternally Inherited Monoallelic Mutations in the KATP Channel Genes</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>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 (KATP 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 KATP 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 KATP channel genes. Sixteen had a paternally derived, monoallelic KATP 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 KATP channel hyperinsulinism (84.2%) demonstrated paternally inherited monoallelic mutations that accurately predicted the presence of the focal form.
Most of the Japanese patients with congenital KATP-channel hyperinsulinism have the focal form.</description><subject>Alleles</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Congenital Hyperinsulinism - genetics</subject><subject>Congenital Hyperinsulinism - metabolism</subject><subject>Congenital Hyperinsulinism - surgery</subject><subject>DNA</subject><subject>DNA Mutational Analysis</subject><subject>Exons</subject><subject>genomics</subject><subject>Humans</subject><subject>Infant</subject><subject>Infants</subject><subject>Islets of Langerhans</subject><subject>KATP Channels - genetics</subject><subject>KATP Channels - metabolism</subject><subject>Lasers</subject><subject>Microdissection</subject><subject>Mutation</subject><subject>Nucleotide sequence</subject><subject>Pancreas</subject><subject>Pancreatectomy</subject><subject>Positron emission tomography</subject><subject>Potassium channels</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EokvLjTPyjV5S_JFsbG6rqF_QVfdQJG7RrDNhvXLsEDtC-8P4fzhquXKyNHrmGet9CfnA2RUXnH0-mivBOCu4UPwVWXFdVkXNdf2arBgTvNC1-HFG3sV4ZIyXZSXfkjPBdClrxVfkzzY4NLODiYLvaOOstwYc3Xhwp2gjDT39CiN4jEh3kCz6FOlvmw50h1MGUh7QJvif6G3Ki3enESfr47yY4vCF7ibswmA9eIOLLUtwynZ3ovf-kNmEHd0GH_IInTV0O6d8J_hIrafpgPTb5mlHmwN4j47eYv7KBXnTg4v4_uU9J99vrp-au-Lh8fa-2TwUKJhIhVHIWcWqrlZojJaw7mpUABXXwCvJK9Mp2K-VFlj1igHT-66EUvZr0KaCXp6TT8_ecQq_ZoypHWw06FzOI8yxVUIorSUXmbz8L8kZr7XiTMiMfnxB5_2AXTtOdoDp1P4rJQPyGUDfBZPDxHHCGNtjmJfgFlm7VN8eTbtU3y7Vy78-MaLk</recordid><startdate>201101</startdate><enddate>201101</enddate><creator>Yorifuji, Tohru</creator><creator>Kawakita, Rie</creator><creator>Nagai, Shizuyo</creator><creator>Sugimine, Akinori</creator><creator>Doi, Hiraku</creator><creator>Nomura, Anryu</creator><creator>Masue, Michiya</creator><creator>Nishibori, Hironori</creator><creator>Yoshizawa, Akihiko</creator><creator>Okamoto, Shinya</creator><creator>Doi, Ryuichiro</creator><creator>Uemoto, Shinji</creator><creator>Nagasaka, Hironori</creator><general>Endocrine Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>201101</creationdate><title>Molecular and Clinical Analysis of Japanese Patients with Persistent Congenital Hyperinsulinism: Predominance of Paternally Inherited Monoallelic Mutations in the KATP Channel Genes</title><author>Yorifuji, Tohru ; Kawakita, Rie ; Nagai, Shizuyo ; Sugimine, Akinori ; Doi, Hiraku ; Nomura, Anryu ; Masue, Michiya ; Nishibori, Hironori ; Yoshizawa, Akihiko ; Okamoto, Shinya ; Doi, Ryuichiro ; Uemoto, Shinji ; Nagasaka, Hironori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e202t-c8e10505d78ecc93a6d7e8aa519a15315cd8ab6892e5f80a09bd4a43f6a9c5af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alleles</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Congenital Hyperinsulinism - genetics</topic><topic>Congenital Hyperinsulinism - metabolism</topic><topic>Congenital Hyperinsulinism - surgery</topic><topic>DNA</topic><topic>DNA Mutational Analysis</topic><topic>Exons</topic><topic>genomics</topic><topic>Humans</topic><topic>Infant</topic><topic>Infants</topic><topic>Islets of Langerhans</topic><topic>KATP Channels - genetics</topic><topic>KATP Channels - metabolism</topic><topic>Lasers</topic><topic>Microdissection</topic><topic>Mutation</topic><topic>Nucleotide sequence</topic><topic>Pancreas</topic><topic>Pancreatectomy</topic><topic>Positron emission tomography</topic><topic>Potassium channels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yorifuji, Tohru</creatorcontrib><creatorcontrib>Kawakita, Rie</creatorcontrib><creatorcontrib>Nagai, Shizuyo</creatorcontrib><creatorcontrib>Sugimine, Akinori</creatorcontrib><creatorcontrib>Doi, Hiraku</creatorcontrib><creatorcontrib>Nomura, Anryu</creatorcontrib><creatorcontrib>Masue, Michiya</creatorcontrib><creatorcontrib>Nishibori, Hironori</creatorcontrib><creatorcontrib>Yoshizawa, Akihiko</creatorcontrib><creatorcontrib>Okamoto, Shinya</creatorcontrib><creatorcontrib>Doi, Ryuichiro</creatorcontrib><creatorcontrib>Uemoto, Shinji</creatorcontrib><creatorcontrib>Nagasaka, Hironori</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yorifuji, Tohru</au><au>Kawakita, Rie</au><au>Nagai, Shizuyo</au><au>Sugimine, Akinori</au><au>Doi, Hiraku</au><au>Nomura, Anryu</au><au>Masue, Michiya</au><au>Nishibori, Hironori</au><au>Yoshizawa, Akihiko</au><au>Okamoto, Shinya</au><au>Doi, Ryuichiro</au><au>Uemoto, Shinji</au><au>Nagasaka, Hironori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular and Clinical Analysis of Japanese Patients with Persistent Congenital Hyperinsulinism: Predominance of Paternally Inherited Monoallelic Mutations in the KATP Channel Genes</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2011-01</date><risdate>2011</risdate><volume>96</volume><issue>1</issue><spage>E141</spage><epage>E145</epage><pages>E141-E145</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>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 (KATP 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 KATP 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 KATP channel genes. Sixteen had a paternally derived, monoallelic KATP 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 KATP channel hyperinsulinism (84.2%) demonstrated paternally inherited monoallelic mutations that accurately predicted the presence of the focal form.
Most of the Japanese patients with congenital KATP-channel hyperinsulinism have the focal form.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>20943781</pmid><doi>10.1210/jc.2010-1281</doi></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Alleles Asian Continental Ancestry Group - genetics Congenital Hyperinsulinism - genetics Congenital Hyperinsulinism - metabolism Congenital Hyperinsulinism - surgery DNA DNA Mutational Analysis Exons genomics Humans Infant Infants Islets of Langerhans KATP Channels - genetics KATP Channels - metabolism Lasers Microdissection Mutation Nucleotide sequence Pancreas Pancreatectomy Positron emission tomography Potassium channels |
| title | Molecular and Clinical Analysis of Japanese Patients with Persistent Congenital Hyperinsulinism: Predominance of Paternally Inherited Monoallelic Mutations in the KATP Channel Genes |
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