家族性复发性葡萄胎存在遗传异质性

Genetic heterogeneity for familial recurrent hydatidiform mole

目的确定家族性复发性葡萄胎(familial recurrent hydatidiform mole ,FRHM)的染色体亲源性,并进行基因定位。方法对葡萄胎组织进行病理分析,并通过激光捕获显微切割(laser capture microdissec-tion,LCM)技术从蜡块组织切片中纯化葡萄胎组织,应用聚合酶链反应扩增微卫星标记,确定FRHM的染色体亲源性;用19q13 .4区域的25个微卫星标记进行单倍型检测,确定这两个家系中致病基因是否为已报道的基因座。结果两个FRHM均为双亲来源的完全性葡萄胎(biparental complete hydatidiform mole ,BiCHM) ,两个家系中的患者在19q13 .4区域中的大多数遗传标记位点上表现为杂合。结论 FRHM常常与BiCHM相关,这两例家系的致病基因不在19q13 .4区域,FRHM存在遗传异质性。

Objective To determine the parental origin of the genome in the molar pregnancies of two familes with familial recurrent hydatidiform mole （FRHM） and to investigate whether the gene responsible for FRHM is likely to be located within the 19q13.4 region in these familes. Methods The features of complete hydatidiform mole （CHM） were confirmed by pathological examination. DNA of CHM was prepared from sections of formalin-fixed paraffin-embedded blocks of molar tissue following laser capture microdissection. The polymerace chain reaction was used to amplify microstellite polymorphisms in DNA from the patients, their husbands and the captured molar tissue. Parental contributions to the molar tissue were detetmined using ABI 310 GeneScan software. Genotyping and haplotype analysis of the candidate region on 19q13.4 was performed for members of both families using 25 microsatellite markers. Results One CHM from each family was identified as a biparental complete hydatidiform mole. All patients were heterozygous for most of the markers in the chromosome region of interest. In addition the two affected sisters in one of the families had different genotypes for the 19q13.4 region, suggesting that mutations in a different locus might be responsible for the disorder in this family. Conclusion The location of the gene responsible for FRHM is unlikely to be located in the 19q13.4 chromosomal region in these two families suggesting that FRHM shows genetic heterogeneity.