Eight novel mutations of theFBN1 gene found in Japanese patients with Marfan syndrome
2000; Wiley; Volume: 17; Issue: 1 Linguagem: Inglês
10.1002/1098-1004(2001)17
ISSN1098-1004
AutoresRitsu Matsukawa, Kazuki Iida, Masako Nakayama, Tsunehiro Mukai, Yutaka Okita, Motomi Ando, Shinichi Takamoto, Nobuyuki Nakajima, Hiroko Morisaki, Takayuki Morisaki,
Tópico(s)Peptidase Inhibition and Analysis
ResumoMarfan syndrome (MFS), an autosomal dominant connective tissue disorder, is caused by mutations in the gene encoding fibrillin 1 (FBN1). The clinical spectrum and severity of MFS disorder varies greatly both between and within families. Since there have been only a few reports on the relationship between FBN1 genotypes and clinical phenotypes in Japanese patients, the FBN1 gene was analyzed in 27 Japanese patients diagnosed with MFS. The nucleotide sequence of the 65 exons of the FBN1 gene was analyzed by PCR and direct sequencing. We have identified six polymorphisms and nine mutations including: four missense mutations (C1652Y, Q2054P, D2127Y, C2221R) in six patients, three nonsense mutations (R215X, S813X, R2220X) in three patients, and two frameshift mutations (2567insT, 7790insT) in three patients. Six of these nine mutations were in the calcium-binding epidermal growth factor-like domains all causative mutations detected except for C2221R were novel. It has been reported that the severe phenotypes of infantile MFS correlate with mutations in the mid region of FBN1, however, mutations were not detected in this region in the population analyzed in this study. Our results suggest that the location of the mutation is not the sole determinant of phenotypic severity; rather there is some difference in the genetic basis of MFS between Japanese and Caucasian populations.
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