{"created":"2023-05-15T09:08:38.016709+00:00","id":16279,"links":{},"metadata":{"_buckets":{"deposit":"e7bb4aae-e12c-407d-81f2-37d75326be49"},"_deposit":{"created_by":15,"id":"16279","owners":[15],"pid":{"revision_id":0,"type":"depid","value":"16279"},"status":"published"},"_oai":{"id":"oai:sapmed.repo.nii.ac.jp:00016279","sets":["1658:1766:1852"]},"author_link":["31771","31772","31773","31774","31775","31776","31765","31766","31767","31768","31769","31770"],"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2001-03","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"67","bibliographicPageStart":"61","bibliographicVolumeNumber":"4","bibliographic_titles":[{"bibliographic_title":"札幌医科大学保健医療学部紀要 = Bulletin of School of Health Sciences Sapporo Medical University"},{"bibliographic_title":"Bulletin of School of Health Sciences Sapporo Medical University","bibliographic_titleLang":"en"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Ｘ連鎖性劣性遺伝形式をとり、出生時より発症するＸ-linked myotubular myopathy（XLMTM）は、重度の筋緊張低下と筋力低下、呼吸障害により人工呼吸管理を必要とし、運動発達も遅延する予後不良の疾患である。myotubularin gene（MTM1遺伝子）により発現する蛋白質myotubularinは、ヒトの筋組織に散在し、tyrosin phosphataseと相同性を有するが、既知の蛋白質ではなく、その機能についても不明である。XLMTMの原因遺伝子（MTM1遺伝子）はX染色体長腕部（Xq28）に位置し、15個のエクソンから構成されることが解明されており、この領域の遺伝子変異がXLMTMの発症に関わることが近年報告された。今回我々は、臨床症状、筋組織学的所見、遺伝子解析によりXLMTMと診断された２症例を報告する。症例１はMTM1遺伝子のエクソン４において193から196の４塩基（AAAG）の欠失を認めた。このためフレームシフト変異を生じ、その後方25番目のアミノ酸がストップコドンとなっていた。母親はこの欠失遺伝子と正常遺伝子をヘテロ接合体として有する保因者と診断された。症例２はエクソン３の塩基163CがTに置換し、このためCGAがTGA（ストップコドン）となるナンセンス変異であった。この症例の母親と一卵性の姉は、同一の変異遺伝子と正常遺伝子をヘテロ接合体として有する保因者と診断された。これらの遺伝子異常によって、この遺伝子によりコードされているmyotubularinの酵素活性の低下が発症の原因である可能性を考察した。X-linked recessive myotubular myopathy （XLMTM） is a congenital myopathy characterized by severe hypotonia and muscle weakness, and respiratory insufficiency after birth. Surviving patients have prolong ventilator dependence and severely delayed motor milestones. Myotubularin, which is encoded by MTM1 gene, is a new family of putative tyrosine phosphatase and appears to be ubiquitously expressed, with a 3.9 kb transcript detected in all adult and fetal tissues studied. We present clinical, histological, and molecular analysis of two patients with XLMTM in which we identified mutations of the MTM1 gene. In one patient, an AAAG deletion was identified at the position of nucleotide 193 in coding exon 4. These 4 bp deletions caused a shift of the reading frame and created a stop codon （frameshift mutation）. His mother had both normal and mutant alleles heterozygously as a XLMTM carrier. In another patient, a C to T substitution of nucleotide 163, leading Arg 55 to stop codon （nonsense mutation） was identified. His mother who was an identical twin, had both normal and mutant alleles heterozygously as a XLMTM carrier. These mutations caused a development of an inactivation of the putative enzymatic activity of myotubularin.","subitem_description_type":"Abstract"}]},"item_7_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"31771","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Naoki, KOZUKA"}]},{"nameIdentifiers":[{"nameIdentifier":"31772","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Nobutada, TACHI"}]},{"nameIdentifiers":[{"nameIdentifier":"31773","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Eiji, UCHIDA"}]},{"nameIdentifiers":[{"nameIdentifier":"31774","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Hidekatsu, TAKEDA"}]},{"nameIdentifiers":[{"nameIdentifier":"31775","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Yasuhito, SENGOKU"}]},{"nameIdentifiers":[{"nameIdentifier":"31776","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Yoshiko, ODANAKA"}]}]},"item_7_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15114/bshs.4.61","subitem_identifier_reg_type":"JaLC"}]},"item_7_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"札幌医科大学保健医療学部"}]},"item_7_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1344-9192","subitem_source_identifier_type":"ISSN"}]},"item_7_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"小塚, 直樹"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"舘, 延忠"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"内田, 英二"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"武田, 秀勝"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"仙石, 泰仁"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"小田中, 芳子"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-09-11"}],"displaytype":"detail","filename":"n13449192461.pdf","filesize":[{"value":"1.2 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"n13449192461.pdf","url":"https://sapmed.repo.nii.ac.jp/record/16279/files/n13449192461.pdf"},"version_id":"ca1dfd7d-e230-4550-b8ae-3438f66ba8d2"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"MTM1遺伝子","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"myotubularin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"遺伝子解析","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"MTM1 gene","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Gene analysis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"X-linked myotubular myopathy","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"X連鎖性劣性遺伝を示したmyotubular myopathyの遺伝子解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"X連鎖性劣性遺伝を示したmyotubular myopathyの遺伝子解析","subitem_title_language":"ja"},{"subitem_title":"Analysis of myotubular myopathy with X-linked recessive trait","subitem_title_language":"en"}]},"item_type_id":"7","owner":"15","path":["1852"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-09-11"},"publish_date":"2019-09-11","publish_status":"0","recid":"16279","relation_version_is_last":true,"title":["X連鎖性劣性遺伝を示したmyotubular myopathyの遺伝子解析"],"weko_creator_id":"15","weko_shared_id":-1},"updated":"2023-12-13T02:55:27.349183+00:00"}