A phenotype of an individual is resulted from an interaction among variants in several genes. Advanced molecular technologies allow us to identify more patients with mutations in more than one genes. Here, we studied a Thai woman with combined clinical features of Marfan (MFS) and Beals (BS) syndromes including frontal bossing, enophthalmos, myopia, the crumpled appearance to the top of the pinnae, midface hypoplasia, high arched palate, dermal stretch marks, aortic enlargement, mitral valve prolapse and regurgitation, aortic root dilatation, and progressive scoliosis. The aortic root enlargement was progressive to a diameter of 7.2 cm requiring an aortic root replacement at the age of 8 years. At her last visit when she was 19 years old, she had moderate aortic regurgitation. Exome sequencing revealed that she carried the c.3159C > G (p.Cys1053Trp) in exon 26 of FBN1 and c.2638G > A (p. Gly880Ser) in exon 20 of FBN2. The variant in FBN1 was de novo, while that in FBN2 was inherited from her unaffected mother. Both genes encode for fibrillins, which are essential for elastic fibers and can form the heterotypic microfibrils. Two defective fibrillins may synergistically worsen cardiovascular manifestations seen in our patient. In this study, we identified the fourth patient with both MFS and BS, carrying mutations in both FBN1 and FBN2.

个体的表型是由几个基因的变体之间的相互作用引起的。先进的分子技术使我们能够识别更多具有多个基因突变的患者。在这里，我们研究了一名具有马凡（MFS）和比尔斯（BS）综合征的临床特征的泰国女性，包括额突，前突，眼睑，近视，耳廓顶部皱纹，中脸发育不全，高弓形arch，皮肤妊娠纹，主动脉扩大，二尖瓣脱垂和返流，主动脉根扩张和进行性脊柱侧弯。主动脉根扩大到直径7.2 cm，需要在8岁时更换主动脉根。在她19岁的最后一次访视时，她患有中度主动脉瓣关闭不全。外显子组测序显示她携带c.3159C> G（p。FBN1和c.2638G> A（第Gly880Ser）中的外显子20 FBN2。FBN1中的变异是从头开始的，而FBN2中的变异是从她未受影响的母亲那里继承的。这两个基因都编码原纤维蛋白，原纤维蛋白对弹性纤维是必不可少的，并且可以形成异型微纤维。两种有缺陷的原纤维蛋白可能协同作用使我们的患者出现心血管疾病。在这项研究中，我们确定了第四名同时患有FBN1和FBN2突变的MFS和BS患者。