Clinical manifestations and genetic analysis of 4 patients with variants of FBN1 gene.
10.3760/cma.j.cn511374-20221212-00866
- Author:
Xin LIU
1
;
Mei YANG
;
Hanbing XIE
;
Qianying ZHAO
;
Bocheng XU
;
Xiao XIAO
;
Yu TAN
;
Shanling LIU
Author Information
1. Key Laboratory of Birth Defects and Related Maternal and Child Diseases of the Ministry of Education, Department of Medical Genetics/Prenatal Diagnosis Center, West China Second Hospital, Sichuan University, Chengdu, Sichuan 610041, China. sunny630@126.com.
- Publication Type:Journal Article
- MeSH:
Female;
Pregnancy;
Humans;
Male;
Exons;
China;
Family;
Genetic Counseling;
Genetic Testing;
Marfan Syndrome/genetics*;
Mutation;
Fibrillin-1/genetics*
- From:
Chinese Journal of Medical Genetics
2023;40(7):781-786
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for four patients suspected for Marfan syndrome (MFS).
METHODS:Four male patients with suspected MFS and their family members who were treated at West China Second Hospital of Sichuan University from September 12, 2019 to March 27, 2021 were selected as the study subjects. Peripheral venous blood samples were collected from the patients and their parents or other pedigree members for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the variants was determined based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).
RESULTS:Genetic testing revealed that all four patients have harbored variants of the FBN1 gene, including c.430_433del (p.His144fs) deletional variant in exon 5, c.493C>T (p.Arg165*) nonsense variant in exon 6, c.5304_5306del (p.Asp1768del) deletional variant in exon 44 and c.5165C>G (p.Ser1722Cys) missense variant in exon 42. According to the ACMG guidelines, the c.430_433del and c.493C>T were classified as pathogenic variants (PVS1+PM2_Supporting+PP4; PVS1+PS1+PS2+PM2_Supporting+PP4). c.5304_5306del and c.5165C>G were classified as likely pathogenic variants (PS2+PM2_Supporting+PM4+PP4; PS2_Moderate+PS1+PM1+PM2_Supporting).
CONCLUSION:The c.430_433del and c.5304_5306del variants of the FBN1 gene identified in this study were unreported previously. Above results have enriched the variation spectrum of the FBN1 gene and provided a basis for genetic counseling and prenatal diagnosis of patients with MFS and acromicric dysplasia.
