Abstract：
Brachyolmia is a rare form of skeletal dysplasia characterized by a wide genetic and clinical heterogeneity. This condition is usually diagnosed postnatally, and very few cases of prenatal diagnosis have been described so far. Here, we report a case of a pregnant woman at 20 weeks\' gestation referred to our center because of fetal short long bones. On targeted ultrasound, mild bowing of the femurs and fibulae and mild micrognathia were also observed. Exome sequencing analysis showed the presence in compound heterozygosity of two pathogenic variants-both truncating variants-in the 3-prime-phosphoadenosine 5-prime-phosphosulfate synthase 2 (PAPSS2) gene, known to cause brachyolmia type 4 (OMIM #612847). Of note, all of the few cases reported prenatally have indeed truncating variants. Hence, we speculate this kind of variant is likely responsible for a complete loss of function of the protein leading to an earlier and more severe phenotype.
摘要：
Brachyolmia是一种罕见的骨骼发育不良，其特征是广泛的遗传和临床异质性。这种情况通常在产后诊断，到目前为止，很少有产前诊断病例被描述。这里,我们报告了一例妊娠20周的孕妇，因为胎儿长骨短而转诊到我们中心。在靶向超声上，还观察到股骨和腓骨的轻度弯曲和轻度的小颌畸形。外显子组测序分析显示在3-prime-磷酸腺苷5-prime-磷酸硫酸合酶2（PAPSS2）基因中存在两种致病变体-两种截短变体的复合杂合性，已知会导致短裂症4型(OMIM#612847)。值得注意的是，产前报告的所有少数病例确实具有截断变异。因此，我们推测这种变异可能是导致蛋白质功能完全丧失的原因，导致更早和更严重的表型。
