CYTOGENETIC AND MOLECULAR ANALYSIS IN INTRAUTERINE FETAL DETERDATION

# 1。本研究对在长崎大学附属医院就诊的IUGR550孕妇进行胎儿生长情况的超声筛查，并对其进行宫内生长迟缓（IUGR）的检测。同时通过CTG、超声检查及子宫动脉、脐动脉血流检查了解IUGR的发病机制。本研究纳入了17例未知的IUGR病例，因为他们的生长迟缓程度小于- 2SD，其IUGR的发病机制尚不清楚。本项目已获得长崎大学伦理委员会的批准。收集了上述17例未知病例的胎盘组织、母亲和父亲的血液样本。此外，为了这项研究，还保留了正常对照组的胎盘组织、母亲和父亲的血液样本。筛选限制性胎盘嵌合体（CPM）从胎儿血液和胎盘进行细胞遗传学研究。17例患者中有3例存在细胞遗传学异常。17例中有2例仅在胎盘中有细胞遗传学异常，而在胎血中没有（受限的胎盘嵌合）。其余12例无细胞遗传学异常的2例被诊断为Russell Silver综合征。Russell Silver综合征可能是由位于7号染色体上的印迹基因缺陷引起的，这表明在这些表现出Russell Silver综合征表型的病例中可能会发生染色体异常，如单亲二体（UPD）。本项目检测到的CPM核型分别为47、XX、+22/46、XX和47、XX、+7/46、XX。这两个病例中检测到的IUGR有可能是由UPD引起的。因此，我们选择了覆盖整个22号染色体和7号染色体的高多态性微卫星标记。通过这些标记物，我们研究了这两例CPM患者是否存在UPD。然而，本研究未检测到UPD，提示未知的严重IUGR是由镶嵌性胎盘缺乏引起的，而不是UPD。本研究提示，一些未知的严重IUGR（小于-2SD）可能是由细胞遗传学和/或遗传异常引起的。对未知重症IUGR的细胞遗传学和遗传学筛查可能会为我们找到解决未知重症IUGR发病机制的线索

#1. Diagnosis and Management of IUGR550 pregnant women treated in Nagasaki University Hospital were screened for their fetal growth by using ultra sonography and then intrauterine growth retardation (IUGR) were detected in this study. Also, CTG, ultrasonography and flow volume of uterine artery and umbilical artery were investigated to know the pathogenesis of IUGR. 17 unknown cases of IUGR were included in this study because they showed less than - 2SD degree of growth retardation and their pathogenesis of IUGR were still unknown.#2. SamplingThis project had obtained a nagasaki university ethical committee's aprroval. Placenta tissues, mather's and father's blood samples were collected from above 17 unknown cases. Also, placenta tissues, mather's and father's blood samples from normal control were preserved for this study.#3. screening of confined placental mosaicism (CPM)Cytogenetic studies from fetal blood and placentas were done. Three of 17 cases had cytogenetic abnormalities in b … More oth fetal blood and placenta. Two of 17 cases had cytogenetic abnormalities only in placenta but not in fetal blood (confined placental mosaicism). Two cases of remaining 12 cases who had no cytogenetic abnormalities were diagnosed phenotypically as a Russell Silver Syndrome. Russell Silver Syndrome may be caused by a deficit of imprinted gene located on chromosome 7, suggesting chromosomal abnormalities such as uniparental disomy (UPD) would be happened in these cases who showed the phenotypes of Russell Silver Syndrome.#4. Screening of UPDThe karyotype of CPM detected in this project were 47, XX, +22/46, XX and 47, XX, +7/46, XX. There was a possibility that IUGR detected in these two cases might be caused by UPD. Therefore, we choosed highly polymorphic microsatellite markers in Japanese, which were covering entire chromosome 22 and chromosome 7. By using these markers, we investigated if UPD was existing in these two cases with CPM or not. However, no UPD was detected in this study, suggesting that unknown severe IUGR was caused by rather placental deficiency due to mosaicism than UPD.In this study, it is suggested that some of unknown severe IUGR (less than -2SD) may be caused by cytogenetic and/or genetic abnormalities. Cytogenetic and genetic screening against unknown severe IUGR may leads us to find a clue to resolve the mechanism of unknown severe IUGR Less