／【Ｋ：】Ｓｅｒｖｅｒ／１６０１０４４６ 新潟県厚生農業協同組合／本文／６０‐４０

五十嵐

１１５‐１１７

2016.02.12 0

A case of the intrauterine fetal death（IUFD）in２７-weeks of gestation induced by the mutation
厚生連医誌of myocardial第Na+２
５巻pump１号
α subunit
１
１５〜
gene
１
１７SCN
２０５
１６
A

Brief report

A case of the intrauterine fetal death（IUFD）in ２
７-weeks ofgestation induced by the mutation of myocardial Na+ pump
α subunit gene SCN５A
Nagaoka Central General Hospital, Department of pathology ; Pathologist

Toshihiko Ikarashi
Backgroud : Concerning the intrauterine fetal death of unknown etiology, we discussed the cardiac sudden
death by the genetic study.
Case report : The formalin-fixed placenta（FFPE）was examined by followings :（i）routine pathologic
study, （ii）infection by PCR and immunostain,（iii）chromosomal pattern by fluorescence in situ
hybridization（FISH）,（iv）myocardial Na+ pump
α subunit gene SCN５A mutation by polymerase
chain reaction-single strand conformational polymorphism（PCR-SSCP）. Positive examination results were mosaic XY/XXY, mutation of exon ２０in SCN５A, cytomegalovirus infection（CMV）,marginal insertion of umbilical cord, and intrauterine growth retardation（IUGR）.
Conclusion : IUFD was directly induced by genetic mutation of SCN５A.
Key words : placenta, intrauterine fetal death（IUFD）, genetic analysis, myocardial Na+ pump α subunit
gene SCN５A mutation, cardiac sudden death, genemutation, polymerase chain reaction-single strand
conformational polymorphism（PCR-SSCP）, immunostain, intrauterine growth retardation（IUGR）,
pathology, method

plex virus（HSV）by PCR with both the reagent, usual
PCR method and SYBR method of Mx３０００P Real-Time
QPCR System, Agilent Technologies（Japan branch office）with SYBR Premix Ex Taq（Tli RNaseH Plus）,Takara（Japan）, and（４）（iii）chromosomal pattern of＃１３, １８, ２
１, and XY by fluorescence in situ hybridization（FISH）（４）,（iv）myocardial Na+ pump α subunit
gene SCN５A mutation by polymerase chain reaction-single strand conformational polymorphism（PCR-SSCP）（５）,.
Pathologic findings were as followings : IUGR
（６６０g, male）, marginal insertion of umbilical cord, suggesting intraplacental fetal circulatory disturbance（Table１）. Genetic examination showed mosaic XY/XXY, mutation of exon ２０ in SCN５A, and intrauterine infection withCMV（Table １）. SCN５A mutation suggested cardiac circulatory disturbance（Table１）.

Conclusion
IUFD was induced by genetic mutation, including
SCN５A.

References
Introduction
In IUFD ２５％ of causes and background factors
were unclear（１）. Routine placental analysis often failed todisclose the cause of IUFD. We have tried to investigate
the true causes with genetic studies ; FISH, PCR, andPCR-SSCP. Genetic mutation of cardiac sudden death wassuggested and reported in this paper.

Case report
Placenta of IUFD in２７-weeks of gestation was pathologically examined and its FFPE specimen was genetically analyzed（１-３）. Genetic analysis was followings :（i）macroscopic and microscopic analysis（１-３）,（ii）infection of CMV, Ebstein-Barr virus（EBV）, Herpes sim-

１．Ikarashi, T. Clinical Obstetric and Gynecologic Pa９９３.
thology ABC.３rd ed. Nagaoka : Pimento ;１
２．Ikarashi, T. Placenta, accessory organs, abortus, neonatal classification. Available from ; URL : http : //www.nrec.sakura.ne.jp/sub２１.htm ; http : //nrec.we.fc２.
com/
３．Ikarashi, T. Placental pathology, standardization ofpathological examination with simplified assessment table. Niigata-Ken Koseiren Med J ２０１４;２３:９
７-１０
７.
Available from ; URL : http : //www.janiigata.sakura.
ne.jp/JMNK/２３-１/２０.pdf
４．Ikarashi, T et al. Establishment of the pathologicaldiagnostic method of total hydatidiform moles by p５７
Kip２ immunostain and fluorescence in situ hybridization for sex chromosomes（XY-fluorescence in situ hybridization, XY-FISH）. Niigata-Ken Koseiren Med J
２０１１;２０:８
３-４. Available from ; URL : http : //www.

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／【Ｋ：】Ｓｅｒｖｅｒ／１６０１０４４６ 新潟県厚生農業協同組合／本文／６０‐４０

厚生連医誌

第２５巻

五十嵐

１１５‐１１７

2016.02.12 0１号 １
１５〜１１７ ２０１
６janiigata.sakura.ne.jp/JMNK/２０-１/０８
３-０８
４.pdf
５．Ikarashi, T. Genetic analysis of the myocardial Na+
pump α subunit gene SCN５A mutation in ７ cases ofsudden death among ４２５ cases of our autopsy cases gene mutation was suggested in ４ cases by polymerase
chain reaction-single strand conformational polymorphism（PCR-SSCP）method. Niigata-Ken Koseiren Med
J２０１５;２４:１-４. Available from ; URL : http : //www.
janiigata.sakura.ne.jp/JMNK/２４-１/００
１-００４.pdf

和 文 抄

録

症例報告
心筋ナトリウムポンプ SCN５A 遺伝子変異による在胎
２７週の子宮内胎児死亡の１症例
長岡中央病院、病理部；病理医
いか らしとしひこ

五十嵐俊彦

背景：原因不明の子宮内胎児死亡（IUFD）の死因検索として、心筋ナトリウムポンプ遺伝子の変異を検討した。
症例内容：ホルマリン固定の胎盤に関して以下の検討を 加 え た：（１）
FISH に よ る 染 色 体 検 査、（２）PCR-SSCP による心筋ナトリウムポンプ SCN５
A 遺伝子変異、（３）
PCR と免疫染色による感染症の有無、そして（４）病理検査が実施された。
その結果、モザイク XY/XXY、SCN５A エクソン２０の変異、サイトメガロウイルス感染、子宮内胎児発育遅延（IUGR）、および臍帯辺縁付着が指摘された。
結論：本 IUFD の直接原因として、心筋ナトリウムポンプ遺伝子等の変異が指摘された。
キーワード：子宮内胎児死亡（IUFD）、遺伝子検査、
心筋ナトリウムポンプ遺伝子 SCN５A 変異、心筋性突然死、遺伝子変異、ポリメラーゼ連鎖反応―一本鎖高 次 構 造 多 型 法（PCR-SSCP）、免疫染色、子宮内胎児発育遅延（IUGR）、病理検査

Table１. Examination results

Table２. Abbreviation― 116 ―

／【Ｋ：】Ｓｅｒｖｅｒ／１６０１０４４６ 新潟県厚生農業協同組合／本文／６０‐４０

五十嵐１１５‐１１７

2016.02.12 0

A case of the intrauterine fetal death（IUFD）in２７-weeks of gestation induced by the mutation of myocardial Na+ pump α subunit gene SCN５AFigure. exon２０of SCN５A in PCR-SSCP study
left : left lane : marker, middle lane : control, right lane : sample,
right : magnified figure of closed rectangle in left one← : original PCR band,straight bar : SSCP bands（２０１５／０８／２３受付）― 117 ―