Abstract：
Marfan syndrome (MFS) is a hereditary systemic connective tissue disorder with great clinical variability. It is caused by heterozygous pathogenic variants in the FBN1 gene. Cardinal manifestations involve the cardiovascular, ocular, and skeletal systems. Clinical diagnosis is based on the revised Ghent nosology. We present the case of a child with a Marfan systemic score of 9 whose genetic study revealed two pathogenic mosaic frameshift variants in the FBN1 gene. Mosaicism is very rare in patients diagnosed with MFS, and this is the first description of a patient with two pathogenic mosaic variants in the FBN1 gene. Both variants are present in cells derived from ectodermal (buccal swab) and mesodermal (leukocyte) tissues, suggesting a mutation prior to gastrulation. We propose a defective repair of the de novo variant in the complementary strand as the mechanism that led this individual to be a carrier of two different populations of mutant cells carrying adjacent variants.
摘要：
马凡氏综合征（MFS）是一种遗传性系统性结缔组织疾病，具有很大的临床变异性。它是由FBN1基因中的杂合致病变体引起的。主要表现涉及心血管，眼,和骨骼系统。临床诊断基于修订的根特疾病学。我们介绍了一个Marfan系统评分为9的儿童的案例，其遗传研究揭示了FBN1基因中的两个致病性马赛克移码变体。马赛克在诊断为MFS的患者中非常罕见，这是对具有FBN1基因中两种致病性镶嵌变体的患者的首次描述。两种变体都存在于来自外胚层（颊拭子）和中胚层（白细胞）组织的细胞中，提示原肠胚形成前的突变。我们提出了互补链中从头变体的缺陷修复，作为导致该个体成为携带相邻变体的两个不同突变细胞群体的载体的机制。
