Montgomery R A, Geraghty M T, Bull E, Gelb B D, Johnson M, McIntosh I, Francomano C A, Dietz H C
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Am J Hum Genet. 1998 Dec;63(6):1703-11. doi: 10.1086/302144.
Mutations in the FBN1 gene, which encodes fibrillin-1, cause Marfan syndrome (MFS) and have been associated with a wide range of milder, overlap phenotypes. The factors that modulate phenotypic severity, both between and within families, remain to be determined. This study examines the relationship between the FBN1 genotype and phenotype in families with extremely mild phenotypes and in those that show striking clinical variation among apparently affected individuals. In one family, clinically similar but etiologically distinct disorders are segregating independently. In another, somatic mosaicism for a mutant FBN1 allele is associated with subdiagnostic manifestations, whereas germ-line transmission of the identical mutation causes severe and rapidly progressive disease. A third family cosegregates mild mitral valve prolapse syndrome with a mutation in FBN1 that can be functionally distinguished from those associated with the classic MFS phenotype. These data have immediate relevance for the diagnostic and prognostic counseling of patients and their family members.
编码原纤蛋白-1的FBN1基因突变会导致马凡综合征（MFS），并与一系列较轻微的重叠表型有关。调节家族间和家族内表型严重程度的因素尚待确定。本研究考察了具有极其轻微表型的家族以及在明显受影响个体中表现出显著临床差异的家族中FBN1基因型与表型之间的关系。在一个家族中，临床症状相似但病因不同的疾病正在独立分离。在另一个家族中，突变的FBN1等位基因的体细胞镶嵌现象与亚诊断表现相关，而相同突变的种系传递则导致严重且进展迅速的疾病。第三个家族中，轻度二尖瓣脱垂综合征与FBN1基因突变共分离，该突变在功能上可与那些与经典马凡综合征表型相关的突变相区分。这些数据对患者及其家庭成员的诊断和预后咨询具有直接意义。
