Abstract：
Trio exome sequencing was performed on a fetus with bilateral mesomelia of the lower limbs with significant angulation of the tibial bones, micrognathia and hypertelorism detected on ultrasound scan at 19 + 0 weeks gestation. The couple is consanguineous. A homozygous pathogenic frameshift variant in the SMOC1 gene (c.339_340del p.(Phe114Cysfs*40)) was detected and both parents were shown to be heterozygous. Pathogenic variants in the SMOC1 gene are associated with microphthalmia with limb anomalies which multidisciplinary team discussion determined to be causal of the scan anomalies detected. The fetus was also a compound heterozygote for CYP21A2 pathogenic variants, confirming a second diagnosis of non-classical congenital adrenal hyperplasia, which was felt incidental to the scan findings. The risk that this couple\'s next pregnancy would be affected by either of these disorders is 1 in 4 (25%) and demonstrates the importance of genetic diagnoses for the family and implications for future pregnancies.
摘要：
对具有下肢双侧夹层且胫骨成角明显的胎儿进行了Trio外显子组测序，在妊娠19+0周的超声扫描中检测到小颌和远视。这对夫妇是近亲。检测到SMOC1基因中的纯合致病性移码变体（c.339_340delp。（Phe114Cysfs*40）），并且显示两个亲本都是杂合的。SMOC1基因中的致病变异与小眼症伴肢体异常相关，多学科团队讨论确定是检测到扫描异常的原因。胎儿也是CYP21A2致病变种的复合杂合子，确认非经典先天性肾上腺增生的二次诊断，这与扫描结果是偶然的。这对夫妇的下一次怀孕受这些疾病影响的风险是四分之一（25％），这表明了遗传诊断对家庭的重要性以及对未来怀孕的影响。
