马凡氏综合征（MFS）是一种常染色体显性结缔组织疾病，原因是纤维蛋白-1（FBN1）的致病变异，每10,000个个体中就有一个受到影响。我们报告了一名16个月大的女性，其早发性MFS杂合，在FBN1基因内具有11.2kb的从头重复。除了遗传测序和染色体微阵列外，还通过光学基因组作图进一步确认了重复的串联位置。这是报告的第3例FBN1中大量多外显子重复的病例，也是唯一被证实为串联的病例。由于与MFS相关的绝大多数致病变异是点突变，这扩大了已知FBN1致病变异的景观，并支持一致使用基因检测策略，可以检测大，indel型变体。
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder due to pathogenic variants in Fibrillin-1 (FBN1) affecting nearly one in every 10,000 individuals. We report a 16-month-old female with early-onset MFS heterozygous for an 11.2 kb de novo duplication within the FBN1 gene. Tandem location of the duplication was further confirmed by optical genome mapping in addition to genetic sequencing and chromosomal microarray. This is the third reported case of a large multi-exon duplication in FBN1, and the only one confirmed to be in tandem. As the vast majority of pathogenic variants associated with MFS are point mutations, this expands the landscape of known FBN1 pathogenic variants and supports consistent use of genetic testing strategies that can detect large, indel-type variants.
