产前诊断 ABCA12基因变异所致丑角样鱼鳞病1例

Prenatal diagnosis of a fetus with harlequin ichthyosis caused by novel splice-site mutation in ABCA12 gene

本文报告了1例产前超声提示胎儿多发结构异常、经家系全外显子组测序诊断为丑角样鱼鳞病的病例。因孕24周+4超声提示胎儿唇角略外翻,鼻梁低平,下颌略后缩,左耳耳廓小,双足足趾姿势异常进行产前诊断。全基因组拷贝数变异检测提示胎儿及父母样本未检测到染色体非整倍体或100 kb以上已知的、明确致病的基因组拷贝数变异。家系全外显子组测序结果提示胎儿ABCA12基因c.2593-1G>A和c.7444C>T致病性变异,分别遗传自临床表型正常的父母,最终确诊为丑角样鱼鳞病。经充分遗传咨询后,孕28周+4引产后死胎可见全身多发畸形。c.2593-1G>A变异位点未见报道,该位点的发现拓宽了ABCA12基因突变谱。

This article reported a rare case of harlequin ichthyosis which was indicated with multiple structural abnormalities by prenatal ultrasound and diagnosed by trio-based whole-exome sequencing(Trio-WES).Prenatal diagnosis was performed because the ultrasound at 24+4 gestational weeks revealed the fetus presenting with eclabium,flattened nose,short mandible,small auricle and abnormal posture of the toes.Copy number variation sequencing(CNV-seq)showed no chromosome aneuploidy or pathogenic copy number variants over 100 kb in the fetal or parental samples.Trio-WES showed that the fetus carried two heterozygous mutations,c.2593-1G>A and c.7444C>T in ABCA12.Sanger sequencing confirmed that c.2593-1G>A,a previously unreported variant,was paternally inherited and c.7444C>T was maternally inherited.Both parents had normal phenotype.The fetus was finally diagnosed with harlequin ichthyosis.After prenatal counseling,the parents made an informed choice to terminate the pregnancy at 28+4 gestational weeks.The stillborn fetus showed multiple malformations The variants in this case expand the spectrum of variants in ABCA12 gene.