Yapeng Li1, Jianhua Xu2, Mingjie Chen3, Binbin Du1, Qiaoli Li3, Qinghe Xing4, Yanzhou Zhang5. 1. Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 2. Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China. 3. Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. 4. Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address: xingqinghe@hotmail.com. 5. Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: zhangyanzhou2050@sina.com.
Abstract
BACKGROUND: Previous studies demonstrated that patients with different FBN1 mutations often present more considerable phenotypic variation compared to different members of the related family carrying a same mutation. The purpose of our study was to identify pathogenic mutation and provide more information about genotype-phenotypic correlations in a large Chinese family with Marfan syndrome. METHODS: 15 related family members from a Chinese 4-generation pedigree with Marfan syndrome underwent physical, ophthalmologic, radiological and cardiovascular examinations. The propositus has De Bakey III aortic dissection and didn't fulfill the revised Ghent criteria for Marfan syndrome. Nine family members have ectopia lentis and their echocardiogram was normal. Five other family members have no evidence of Marfan syndrome. Genomic DNA was isolated from blood leukocytes. The exome sequencing was employed on the propositus, then the Sanger sequencing was conducted for mutation verification in other 14 participants of this family. RESULTS: The causative mutation in FBN1 discovered in the propositus was a known heterozygous missense mutation, c.1633T>G (p.R545C), in exon 14 (NM 000138). This same mutation was also identified in all 9 ectopia lentis patients and one unaffected 8-year-old girl. However, the same mutation was not discovered in other 4 unaffected family members. CONCLUSIONS: Our data enhance the information of genotype-phenotype correlation owing to FBN1 mutations. To our current knowledge, we firstly reported that the same FBN1 mutation, c. 1633C>T (Arg545Cys), was detected simultaneously in three different cardinal phenotypes (ectopia lentis, aortic dissection and unaffected) within one family. The unaffected girl with FBN1 mutation may presumably represent a rare case of nonpenetrance.
BACKGROUND: Previous studies demonstrated that patients with different FBN1 mutations often present more considerable phenotypic variation compared to different members of the related family carrying a same mutation. The purpose of our study was to identify pathogenic mutation and provide more information about genotype-phenotypic correlations in a large Chinese family with Marfan syndrome. METHODS: 15 related family members from a Chinese 4-generation pedigree with Marfan syndrome underwent physical, ophthalmologic, radiological and cardiovascular examinations. The propositus has De Bakey III aortic dissection and didn't fulfill the revised Ghent criteria for Marfan syndrome. Nine family members have ectopia lentis and their echocardiogram was normal. Five other family members have no evidence of Marfan syndrome. Genomic DNA was isolated from blood leukocytes. The exome sequencing was employed on the propositus, then the Sanger sequencing was conducted for mutation verification in other 14 participants of this family. RESULTS: The causative mutation in FBN1 discovered in the propositus was a known heterozygous missense mutation, c.1633T>G (p.R545C), in exon 14 (NM 000138). This same mutation was also identified in all 9 ectopia lentispatients and one unaffected 8-year-old girl. However, the same mutation was not discovered in other 4 unaffected family members. CONCLUSIONS: Our data enhance the information of genotype-phenotype correlation owing to FBN1 mutations. To our current knowledge, we firstly reported that the same FBN1 mutation, c. 1633C>T (Arg545Cys), was detected simultaneously in three different cardinal phenotypes (ectopia lentis, aortic dissection and unaffected) within one family. The unaffected girl with FBN1 mutation may presumably represent a rare case of nonpenetrance.
Authors: Stefanie S Portelli; Elizabeth N Robertson; Cassandra Malecki; Kiersten A Liddy; Brett D Hambly; Richmond W Jeremy Journal: Biophys Rev Date: 2018-09-28
Authors: Yanireth Jimenez; Cesar Paulsen; Eduardo Turner; Sebastian Iturra; Oscar Cuevas; Guillermo Lay-Son; Gabriela M Repetto; Marcelo Rojas; Juan F Calderon Journal: Genes (Basel) Date: 2022-06-08 Impact factor: 4.141