中国汉族两个马凡综合征家系FBN1基因的一个新插入突变 和一个复发点突变.

Objective: To make genetic diagnosis and discuss the clinical characteristics in two Chinese Han Marfan syndrome (MFS) families. Methods: Family investigation and pedigree analysis was earned out in two MFS families. Variants detection for whole exons of FBN1 gene were performed by polymerase chain reaction and DNA direct sequencing. Functional significances for variants were assessed using by Swiss-model. Polyphen-2 and SIFT software. Results: The two families were characterized as an autosomal dominant inheritance. A de novo variant of FBN1 gene, an insertion A at 1691 base of exon 13 was identified in the patients of family 1 (1691 ins A), which resulted in the premature termination of translation at 571 amino acid, hi addition, a known point mutation at exon 27 (3463 G>A) was found in the patients of family 2. which resulted in amino acid change from Asp to Asn at 1155. The two variants were absent in healthy family members and 50 healthy controls. Results of functional significance prediction indicated that these two variants might influence the structure or function of fibrillin-1 protein. Conclusions: A novel insertion variant (1691 ins A) and a known point mutation (3463 G>A) are found in two MFS families. The results enlarge the spectrum of FBN1 gene variants and further support the hypothesis that FBX1 gene variants are pathogenic variants for MFS. [ABSTRACT FROM AUTHOR]