Abstract：
Autosomal recessive ROR2-Robinow syndrome is caused by pathogenic variants in the ROR2 gene. Fetal ultrasound done on our patient at 24 + 3/7 weeks gestation showed macrocephaly, brachycephaly, flat face, prominent forehead, mild frontal bossing, lower thoracic hemivertebrae, digital abnormalities and micropenis. Fetal trio whole exome sequencing done on amniocytes showed two pathogenic compound heterozygous variants in the ROR2 gene, c.1324 C > T; p.(Arg442*) maternally inherited and c.1366dup; p.(Leu456Profs*3) apparently de novo. c.1324 C > T; p.(Arg442*) is a nonsense variant resulting in protein truncation reported to be associated with RRS3. c.1366dup; p.(Leu456Profs*3) is a frameshift variant predicted to result in protein truncation reported to segregate with the disease in multiple affected individuals from a single large family with distal symphalangism of the fourth finger. Fetal autopsy following pregnancy termination showed a large head with low-set ears, facial abnormalities, mesomelic bone shortening, hemivertebra, fused S3 and S4 vertebral bodies, several fused rib heads and short penis with buried shaft.
摘要：
常染色体隐性遗传ROR2-Robinow综合征是由ROR2基因的致病变异引起的。在妊娠24+3/7周时对我们的患者进行的胎儿超声检查显示大头畸形，短头畸形,平坦的脸，突出的前额,轻微的额头带,下胸椎,数字异常和微阴茎。在羊膜细胞上进行的胎儿三人组全外显子组测序显示ROR2基因中的两个致病性复合杂合变体，c.1324C>T；p.（Arg442*）母系遗传和c.1366dup；p.（Leu456Profs*3）显然是从头。c.1324C>T;p.(Arg442*)是无义变体,导致据报道与RRS3相关的蛋白质截短。c.1366dup;p。（Leu456Profs*3）是一种移码变体，预计会导致蛋白质截断，据报道，该蛋白质截断与该疾病隔离在一个大型家庭的多个受影响的个体中，该家庭的第四根手指具有远端共形。终止妊娠后的胎儿尸检显示头部较大，耳朵较低，面部异常,间膜骨缩短，半椎骨,融合的S3和S4椎体，几个融合的肋骨头和短阴茎，埋轴。
