CYTOGENETIC AND MOLECULAR ANALYSIS IN INTRAUTERINE FETAL DETERDATION

1.对长崎大学附属医院收治的胎儿宫内发育迟缓550例进行超声筛查，检测胎儿宫内发育迟缓(IUGR)。同时，对胎儿宫内发育迟缓的发病机制进行CTG、超声检查及子宫动脉、脐动脉血流量的检测。本研究纳入17例不明原因的IUGR患者，其生长发育迟缓程度均小于-2SD，其发病机制尚不清楚。#2.抽样本项目已获得长崎大学伦理委员会批准。从上述17例不明原因病例中采集了胎盘组织、母亲和父亲的血样。同时，保存正常对照的胎盘组织、母亲和父亲的血液样本。#3.从胎儿血液和胎盘中筛选限制性胎盘嵌合体(CPM)细胞遗传学研究。17例中有3例有b-…的细胞遗传学异常。还有更多的胎儿血液和胎盘。17例中有2例仅在胎盘有细胞遗传学异常，而在胎儿血液中无细胞遗传学异常(局限性胎盘嵌合体)。其余12例无细胞遗传学异常的患者中有2例被诊断为Russell Silver综合征。Russell Silver综合征可能是由于7号染色体印记基因缺失所致，提示表现为Russell Silver综合征表型的患者可发生单亲二体(UPD)等染色体异常。#4.UPD的筛选本项目检测到的CPM核型为47，XX，+22/46，XX和47，XX，+7/46，XX。这两例胎儿宫内发育迟缓可能是由UPD引起的。因此，我们选择了覆盖整个22号染色体和7号染色体的日本人高度多态的微卫星标记，通过这些标记，我们调查了这两例CPM患者是否存在UPD。然而，本研究中未检测到UPD，提示不明原因的重度IUGR可能是由嵌合性胎盘缺陷引起的，而不是UPD。对不明原因重度IUGR的细胞遗传学筛选可能会为解决不明原因重度IUGR的发病机制提供线索

#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