Departamento de Genética e Biologia Evolutiva, Instituto de Biociência, Hospital das Clínicas, Universidade de São Paulo.
Braz J Med Biol Res. 2011 Aug;44(8):793-800. doi: 10.1590/s0100-879x2011007500095. Epub 2011 Jul 29.
Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects) who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34) of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.
马凡综合征（MFS）是一种常染色体显性遗传的结缔组织疾病，影响眼、骨骼和心血管系统，临床表现多样。虽然 FBN1 基因突变已被认为是该病的病因，但最近其他基因座也与 MFS 相关，表明该病存在遗传异质性。我们通过对 34 个家族（345 名患者）进行 FBN1 和 TGFBR2 基因的连锁分析，探讨了 MFS 的遗传异质性问题，这些家族均符合根据根特标准制定的疾病临床诊断标准。我们使用了总共 6 个微卫星标记，发现 70.6%（24/34）的家族存在或不能排除与 FBN1 基因的连锁，而在 1 个家族中，MFS 表型与 TGFBR2 基因分离。此外，在 4 个家族中，FBN1 和 TGFBR2 基因的连锁被排除，且 TGFBR1 编码区未发现突变，表明存在其他与 MFS 相关的基因。我们的结果表明，MFS 的遗传异质性可能比以前报道的更大。
