PDF(Pubmed)
Abstract：
Congenital contractural arachnodactyly (CCA) is a rare connective tissue disorder characterized by arachnodactyly, multiple joint contractures, progressive kyphoscoliosis, pectus deformity and abnormal crumpled ears. FBN2 is the only gene currently known to be associated with CCA. In this study, we report on a prenatal case presented with skeletal, cardiac and spinal malformations. And his father had elongated limbs, contractures of the proximal interphalangeal joints, high myopia and scoliosis. We conducted whole exome sequencing (WES) on the fetus-parental trio and a heterozygous variant (hg19 chr5:127,673,685, c.3598 + 4A > G, NM_001999.4) in intron 27 of the FBN2 gene was successfully identified, inherited from the father. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate the potential splicing effect of this variant, which confirmed that the variant caused a deletion of exon 27 (126 bp) by disrupting the splice-donor site and destroyed the 17th calcium-binding epidermal growth factor-like (cbEGF) domain. Our research not only finds the etiology of the disease in affected individuals and expands the mutation spectrum of FBN2 gene, but also provides genetic counseling and fertility guidance for this family.
摘要：
先天性蛛网膜挛缩症（CCA）是一种罕见的结缔组织疾病，以蛛网膜畸形为特征，多发关节挛缩,进行性脊柱侧后凸,胸部畸形和异常皱褶的耳朵。FBN2是目前已知与CCA相关的唯一基因。在这项研究中,我们报道了一个产前骨骼病例，心脏和脊髓畸形.他父亲的四肢拉长，近端指间关节挛缩，高度近视和脊柱侧弯。我们对胎儿亲本三重奏和杂合变体进行了全外显子组测序（WES）（hg19chr5：127,673,685，c.35984A>G，NM_001999.4)在FBN2基因的内含子27中成功鉴定,继承自父亲。进行逆转录聚合酶链反应（RT-PCR）以评估该变体的潜在剪接效果，这证实了该变体通过破坏剪接供体位点而导致外显子27（126bp）的缺失，并破坏了第17个钙结合表皮生长因子样（cbEGF）结构域。我们的研究不仅发现了发病个体的病因,而且扩大了FBN2基因的突变谱,而且还为这个家庭提供遗传咨询和生育指导。
