Whole exome sequencing unravels disease-causing genes in craniofacial fibrous dysplasia with ocular complications

Craniofacial fibrous dysplasia (CFD) is a complex and rare disorder that involves the craniofacial bones. However, CFD with ocular complications as the first symptom is uncommon and easily missed or misdiagnosed in clinical practice. It is currently reported that CFD arises from somatic mutations in GNAS that can be detected using conventional methods, such as MEMO-PCR and PNA-mediated PCR, but not all patients can be identified. We speculated that these methods may be limited in identifying low frequency variants in the GNAS mosaic mutation or additional disease-causing genes may be present in those patients. Thus, we applied whole exome sequencing (WES) as a molecular diagnostic tool to identify causative mutations in CFD.

颅面骨纤维异常增殖症（Craniofacial fibrous dysplasia, CFD）是一类累及颅面骨骼的复杂罕见疾病。以眼部并发症为首发表现的CFD较为少见，临床实践中极易被漏诊或误诊。目前已知CFD的发病与GNAS体细胞突变相关，此类突变可通过MEMO-PCR、PNA介导PCR等常规方法检出，但并非所有患者均可被确诊。我们推测，上述常规检测方法在识别GNAS嵌合突变中的低频变异时存在局限，或此类患者中还存在其他致病基因。为此，我们采用全外显子组测序（WES）作为分子诊断工具，以期明确CFD的致病突变。