An integrated clinical and molecular study of a cohort of Turkish patients with Marfan syndrome harboring known and novel FBN1 variants.
J Hum Genet
; 66(7): 647-657, 2021 Jul.
Article
in En
| MEDLINE
| ID: mdl-33483584
ABSTRACT
Marfan syndrome (MFS) is an autosomal dominant genetic condition that mainly affects connective tissue in many parts of the body. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. The diagnosis of MFS relies on the revised Ghent criteria, outlined by international expert opinion to facilitate accurate recognition of this syndrome as well as to improve patient management and counseling. However, it may not always be possible to make a definitive diagnosis according to these criteria in each patient and thus molecular confirmation is necessary in subjects with suspected MFS. This debilitating, if not fatal, disorder is caused by mutations in FBN1, which encodes a major constitutive element of extracellular microfibrils. Here, we present a detailed clinical and molecular analysis of 76 Turkish patients with definitive or suspected MFS diagnosed at our center between 2014 and 2019. We were able to identify a total of 51 different FBN1 variants in our cohort, 31 of which have previously been reported in the relevant scientific literature. The remaining 20 variants have not been documented to date. In one patient, we detected a large deletion including the entire FBN1 gene using the array CGH approach. Currently, there are very few studies on the genotype-phenotype correlation of patients with MFS, and no clear genotype-phenotype maps for MFS have been constructed so far, except for some cases. We believe that our findings will make a rich and peculiar contribution to the elusive genotype-phenotype relationship in MFS, especially in this large and populous ethnic group.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Predisposition to Disease
/
Genetic Association Studies
/
Fibrillin-1
/
Marfan Syndrome
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2021
Document type:
Article
Affiliation country:
Turkey