Department of Clinical Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Hum Genet. 2011 Mar;19(3):247-52. doi: 10.1038/ejhg.2010.174. Epub 2010 Nov 10.
The most common mutations found in FBN1 are missense mutations (56%), mainly substituting or creating a cysteine in a cbEGF domain. Other mutations are frameshift, splice and nonsense mutations. There are only a few reports of patients with marfanoid features and a molecularly proven complete deletion of a FBN1 allele. We describe the clinical features of 10 patients with a complete FBN1 gene deletion. Seven patients fulfilled the Ghent criteria for Marfan syndrome (MFS). The other three patients were examined at a young age and did not (yet) present the full clinical picture of MFS yet. Ectopia lentis was present in at least two patients. Aortic root dilatation was present in 6 of the 10 patients. In three patients, the aortic root diameter was on the 95th percentile and in one patient, the diameter of the aortic root was normal, the cross-section, however, had a cloverleaf appearance. Two patients underwent aortic root surgery at a relatively young age (27 and 34 years). Mitral valve prolapse was present in 4 of the 10 patients, and billowing of the mitral valve in 1. All patients had facial and skeletal features of MFS. Two patients with a large deletion extending beyond the FBN1 gene had an extended phenotype. We conclude that complete loss of one FBN1 allele does not predict a mild phenotype, and these findings support the hypothesis that true haploinsufficiency can lead to the classical phenotype of Marfan syndrome.
在 FBN1 中最常见的突变是错义突变（56%），主要是在 cbEGF 结构域中取代或产生半胱氨酸。其他突变包括移码、剪接和无义突变。只有少数报道描述了具有马凡样特征和分子证实的 FBN1 等位基因完全缺失的患者。我们描述了 10 例 FBN1 基因完全缺失患者的临床特征。7 例患者符合马凡综合征（MFS）的根特标准。另外 3 例患者在年轻时接受检查，尚未出现 MFS 的完整临床特征。至少有 2 例患者存在晶状体异位。10 例患者中有 6 例存在主动脉根部扩张。在 3 例患者中，主动脉根部直径位于第 95 百分位，在 1 例患者中，主动脉根部直径正常，但横断面呈三叶形。2 例患者在相对年轻的年龄接受了主动脉根部手术（27 岁和 34 岁）。4 例患者存在二尖瓣脱垂，1 例患者存在二尖瓣膨出。所有患者均具有 MFS 的面部和骨骼特征。2 例具有超出 FBN1 基因的大缺失的患者具有扩展表型。我们得出结论，一个 FBN1 等位基因的完全缺失并不预示着轻度表型，这些发现支持了真正的单倍不足可能导致马凡综合征的经典表型的假说。
