Cliffe Simon T, Wong Melanie, Taylor Peter J, Ruga Ezia, Wilcken Bridget, Lindeman Robert, Buckley Michael F, Roscioli Tony
Centre for Vascular Research, University of New South Wales, Sydney, Australia.
Prenat Diagn. 2007 Jul;27(7):674-6. doi: 10.1002/pd.1759.
We present the first prenatal diagnosis of familial hepatic veno-occlusive disease with immunodeficiency (VODI). Homozygous mutations in the gene SP110 are the genetic basis of VODI. The proband in this report presented at three months of age with hepatomegaly hepatic failure and was found to have hypogammaglobulinemia. He died one month after hepatic transplant at eight months of age due to hemophagocytic syndrome. DNA testing detected a homozygous truncating mutation in exon 5; SP110 c.642delC. Prenatal testing was offered to this family in a subsequent pregnancy.
Chorion villus was sampled at 12 weeks' gestation. DNA was extracted using standard techniques, and sequencing of SP110 exon 5 was performed using flanking primers. Maternal contamination was excluded by examining STR markers in CVS and maternal DNA.
A heterozygous SP110 c.642delC mutation was detected in exon 5. This mutation was present in heterozygous form in both parents.
The prenatal test result is predictive of a child with a normal immune and hepatic phenotype. This report presents the first prenatal molecular diagnosis for VODI and shows the importance of molecular genetic research in not only defining the aetiology of syndromes but also in assisting reproductive choices through the collaboration of genetic and feto-maternal services.
我们首次报告了伴有免疫缺陷的家族性肝静脉闭塞病（VODI）的产前诊断。SP110基因的纯合突变是VODI的遗传基础。本报告中的先证者在3个月大时出现肝肿大和肝衰竭，被发现有低丙种球蛋白血症。他在8个月大时肝移植后1个月因噬血细胞综合征死亡。DNA检测在外显子5中检测到一个纯合截短突变；SP110 c.642delC。在随后的妊娠中为这个家庭提供了产前检测。
在妊娠12周时采集绒毛膜绒毛。使用标准技术提取DNA，并使用侧翼引物对SP110外显子5进行测序。通过检测绒毛膜绒毛样本（CVS）和母亲DNA中的STR标记排除母亲污染。
在外显子5中检测到一个杂合的SP110 c.642delC突变。父母双方均以杂合形式存在此突变。
产前检测结果预示胎儿具有正常的免疫和肝脏表型。本报告首次展示了VODI的产前分子诊断，并表明分子遗传学研究不仅在确定综合征病因方面很重要，而且在通过遗传和胎儿-母亲服务的合作协助生殖选择方面也很重要。
