Abstract：
A 19-year-old gravida underwent genetic counseling at the 26th week of gestation due to sonographically detected fetal anomalies, including Dandy-Walker malformation, characterized by cerebellar vermis hypoplasia and an enlarged cisterna magna, and single ventricle heart. Following amniocentesis at the 27th week, after the normal quantitative fluorescence polymerase chain reaction and chromosomal microarray results, trio clinical exome sequencing was performed, revealing a novel homozygous pathogenic variant in the MPDZ gene, c.4576G>T (NM_001378778.1). So far, homozygous and compound heterozygous variants in MPDZ have been strongly linked to congenital hydrocephalus type 2 with or without accompanying brain or eye anomalies. The reported variant, absent in control databases, resulted in premature termination of protein synthesis, consistent with pathogenicity predictions. Both parents were identified as heterozygous carriers. Pregnancy termination was chosen post-diagnosis. Postmortem findings correlated with prenatal ultrasound. Our case broadens the prenatal phenotypic spectrum associated with MPDZ variants, necessitating further studies for comprehensive understanding of molecular mechanisms beneath the clinical manifestations.
摘要：
一名19岁的孕妇在妊娠第26周接受了遗传咨询，原因是超声检查发现胎儿异常，包括Dandy-Walker畸形,以小脑疣发育不全和大脑池增大为特征，和单心室心脏。第27周羊膜穿刺术后,经正常定量荧光聚合酶链反应和染色体微阵列结果,进行了三临床外显子组测序，揭示了MPDZ基因中的一种新的纯合致病变异，c.4576G>T(NM_001378778.1)。到目前为止,MPDZ中的纯合和复合杂合变体与2型先天性脑积水密切相关，伴有或不伴有脑或眼异常。报告的变体，在控制数据库中不存在，导致蛋白质合成的过早终止，与致病性预测一致。两个亲本都被鉴定为杂合携带者。诊断后选择终止妊娠。尸检结果与产前超声相关。我们的病例拓宽了与MPDZ变异相关的产前表型谱，需要进一步研究以全面了解临床表现下的分子机制。
