Booms P, Cisler J, Mathews K R, Godfrey M, Tiecke F, Kaufmann U C, Vetter U, Hagemeier C, Robinson P N
Department of General Pediatrics, Charité, Humboldt University, Berlin, Germany.
Clin Genet. 1999 Feb;55(2):110-7. doi: 10.1034/j.1399-0004.1999.550207.x.
The Marfan syndrome is an autosomal dominant heritable disorder of connective tissue that involves principally the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum, the neonatal Marfan syndrome (nMFS), is characterized by pronounced atrioventricular valve dysfunction, and death often occurs within the first year of life due to congestive heart failure. Mutations in the gene coding for fibrillin-1, FBN1, are known to cause Marfan syndrome, and have been identified in almost all exons of FBN1. Here, we describe a novel mutation affecting the invariant + 1 position of the splice donor site in intron 31, associated with skipping of exon 31, in a patient with nMFS. Published reports of nMFS are reviewed and a strict definition for nMFS is suggested. If this definition is used, all nMFS mutations reported to date lie in one of two hot spots, comprising mainly missense mutations in FBN1 exons 24-27 and mutations causing skipping of exon 31 or 32.
马凡综合征是一种常染色体显性遗传性结缔组织疾病，主要累及骨骼、眼部和心血管系统。新生儿马凡综合征（nMFS）处于该疾病表型谱的最严重一端，其特征为明显的房室瓣功能障碍，常因充血性心力衰竭在出生后第一年内死亡。已知编码原纤维蛋白-1（FBN1）的基因突变会导致马凡综合征，且几乎在FBN1的所有外显子中均已发现此类突变。在此，我们描述了一名nMFS患者中一个影响内含子31剪接供体位点恒定+1位置的新突变，该突变与外显子31跳跃相关。我们对已发表的nMFS报告进行了综述，并提出了nMFS的严格定义。如果采用这一定义，迄今报道的所有nMFS突变均位于两个热点之一，主要包括FBN1外显子24 - 27中的错义突变以及导致外显子31或32跳跃的突变。
