PDF(Pubmed)
Abstract：
BACKGROUND: Mutations in fibrillin-1 (FBN1) are known to be associated with Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Most FBN1 mutations are missense or nonsense mutations. Traditional molecular genetic testing for the FBN1 gene, like Sanger sequencing, may miss disease-causing mutations in the gene\'s regulatory regions or non-coding sequences, as well as partial or complete gene deletions and duplications.
METHODS: Next-generation sequencing, multiplex ligation-dependent probe amplification and gap PCR were conducted on two MFS patients to screen for disease-causing mutations.
RESULTS: We identified two large deletions in FBN1 from two MFS patients. One patient had a 0.23 Mb deletion (NC_000015.9:g.48550506_48779360del) including 5\'UTR-exon6 of FBN1. The other patient harbored a 1416 bp deletion (NC_000015.9:g.48410869_48412284del) affecting the last exon, exon 66, of the FBN1 gene.
CONCLUSIONS: Our results expanded the number of large FBN1 deletions and highlighted the importance of screening for large deletions in FBN1 in clinical genetic testing, especially for those with the classic MFS phenotype.
METHODS: Next-generation sequencing, multiplex ligation-dependent probe amplification and gap PCR were conducted on two MFS patients to screen for disease-causing mutations.
RESULTS: We identified two large deletions in FBN1 from two MFS patients. One patient had a 0.23 Mb deletion (NC_000015.9:g.48550506_48779360del) including 5\'UTR-exon6 of FBN1. The other patient harbored a 1416 bp deletion (NC_000015.9:g.48410869_48412284del) affecting the last exon, exon 66, of the FBN1 gene.
CONCLUSIONS: Our results expanded the number of large FBN1 deletions and highlighted the importance of screening for large deletions in FBN1 in clinical genetic testing, especially for those with the classic MFS phenotype.
摘要：
背景：已知纤丝蛋白-1（FBN1）的突变与马凡氏综合征（MFS）有关，常染色体显性结缔组织疾病。大多数FBN1突变是错义或无义突变。传统的FBN1基因分子基因检测，比如Sanger测序,可能错过基因调控区或非编码序列中的致病突变，以及部分或完全的基因缺失和重复。
方法：下一代测序，对2例MFS患者进行多重连接依赖性探针扩增和gapPCR,筛选致病突变.
结果：我们从两名MFS患者中发现了两个大的FBN1缺失。一名患者有0.23Mb缺失（NC_000015.9：g.48550506_48779360del），包括FBN1的5'UTR-exon6。另一名患者携带影响最后一个外显子的1416bp缺失(NC_000015.9:g.48410869_48412284del)，外显子66，FBN1基因。
结论：我们的结果扩大了FBN1大缺失的数量，并强调了在临床基因检测中筛查FBN1大缺失的重要性。特别是对于那些具有经典MFS表型的人。
方法：下一代测序，对2例MFS患者进行多重连接依赖性探针扩增和gapPCR,筛选致病突变.
结果：我们从两名MFS患者中发现了两个大的FBN1缺失。一名患者有0.23Mb缺失（NC_000015.9：g.48550506_48779360del），包括FBN1的5'UTR-exon6。另一名患者携带影响最后一个外显子的1416bp缺失(NC_000015.9:g.48410869_48412284del)，外显子66，FBN1基因。
结论：我们的结果扩大了FBN1大缺失的数量，并强调了在临床基因检测中筛查FBN1大缺失的重要性。特别是对于那些具有经典MFS表型的人。
