University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Am J Med Genet A. 2024 Feb;194(2):368-373. doi: 10.1002/ajmg.a.63440. Epub 2023 Oct 15.
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.
马凡综合征（MFS）是一种常染色体显性结缔组织疾病，由 Fibrillin-1（FBN1）中的致病变异引起，几乎每 10000 人中就有 1 人受到影响。我们报告了一例 16 个月大的女性，患有早发型 MFS，杂合子中存在 FBN1 基因内 11.2kb 的从头重复。重复的串联位置通过光学基因组图谱进一步确认，除了遗传测序和染色体微阵列。这是第三个报道的 FBN1 中大型多外显子重复的病例，也是唯一一个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 致病变异的范围，并支持一致使用能够检测大的、缺失型变异的遗传检测策略。
