Genotype–Phenotype Correlation in Patients with Suspected Marfan Syndrome a Single-Center Experience

Year 2025, Volume: 11 Issue: 4, 411 - 421, 30.11.2025

Çağrı Doğan , Elif Doğan , Taner Kasar

https://doi.org/10.19127/mbsjohs.1800242

Abstract

Objective: This study aimed to investigate genotype–phenotype correlations in patients with a clinical suspicion of Marfan syndrome and to identify novel FBN1 variants contributing to disease heterogeneity within a Turkish cohort.
Method: A total of 81 patients referred to the Medical Genetics Department of Ordu University Hospital with suspected Marfan syndrome were evaluated according to the revised Ghent criteria. Genomic DNA was extracted from peripheral blood samples, and all exons of the FBN1 gene were analyzed using next-generation sequencing on the Illumina MiSeq platform. Detected variants were interpreted through multiple databases including ClinVar, HGMD, VarSome, and Franklin, and classified according to ACMG guidelines.
Results: Among 81 patients (49 males, 32 females; mean age 35 years), four were found to harbor FBN1 variants consistent with the Marfan phenotype. Two novel variants—c.6680C>T (p.Gly1668Ala) and c.288del (p.Arg96Serfs*12)—were identified and classified as likely pathogenic. Two additional variants—c.176G>C (p.Cys59Ser) and c.5003_5004delinsCT (p.Ser2227Leu)—were previously reported but redefined with new phenotypic associations. Cardiovascular findings included aortic root dilatation and mitral valve prolapse, while ocular manifestations (ectopia lentis, myopia) and skeletal features (arachnodactyly, scoliosis, joint hypermobility) were predominant.
Conclusion: This study expands the known FBN1 mutation spectrum in Marfan syndrome and reinforces the significance of comprehensive molecular testing combined with clinical evaluation for accurate diagnosis. The identification of novel and rare variants highlights the genetic diversity of Marfan syndrome in the Turkish population and underscores the need for continuous genotype–phenotype mapping to improve patient management and genetic counseling.

Keywords

marfan syndrome , FBN1 gene , Genotype–Phenotype Correlation , next generation sequencing

Ethical Statement

Our study was conducted with the approval of the Non-Interventional Clinical Research Ethics Committee of Ordu University (Decision No: 2025/308).

Supporting Institution

This study did not receive any support from any institution or organization.

Marfan Sendromu Şüphesi Olan Hastalarda Genotip–Fenotip Korelasyonu: Tek Merkezli Bir Deneyim

Abstract

Amaç:
Bu çalışmanın amacı, Marfan sendromu ön tanısı ile değerlendirilen hastalarda genotip–fenotip korelasyonlarını araştırmak ve Türk kohortunda hastalığın heterojenitesine katkı sağlayan yeni FBN1 varyantlarını belirlemektir.
Yöntem:
Marfan sendromu şüphesiyle Ordu Üniversitesi Tıp Fakültesi Tıbbi Genetik Anabilim Dalı’na yönlendirilen toplam 81 hasta, revize edilmiş Ghent kriterlerine göre değerlendirildi. Periferik kandan elde edilen genomik DNA örnekleri Illumina MiSeq platformunda yeni nesil dizileme yöntemiyle analiz edildi. Saptanan FBN1 gen varyantları ClinVar, HGMD, VarSome ve Franklin veritabanları aracılığıyla değerlendirildi ve ACMG kriterlerine göre sınıflandırıldı.
Bulgular:
Seksen bir hastanın (49 erkek, 32 kadın; ortalama yaş 35) dördünde Marfan fenotipiyle uyumlu FBN1 varyantları saptandı. İki yeni varyant—c.6680C>T (p.Gly1668Ala) ve c.288del (p.Arg96Serfs*12)—tanımlandı ve “muhtemel patojenik” olarak sınıflandırıldı. İki ek varyant—c.176G>C (p.Cys59Ser) ve c.5003_5004delinsCT (p.Ser2227Leu)—daha önce raporlanmış olmakla birlikte yeni fenotipik bulgularla ilişkilendirildi. Kardiyovasküler bulgular arasında aort kökü dilatasyonu ve mitral kapak prolapsusu yer alırken, oküler (ektopia lentis, miyopi) ve iskelet sistemi bulguları (araknodaktili, skolyoz, eklem hipermobilitesi) baskındı.
Sonuç:
Bu çalışma, Marfan sendromundaki bilinen FBN1 mutasyon spektrumunu genişletmekte ve doğru tanı için moleküler analizlerin klinik değerlendirme ile birlikte kullanılmasının önemini vurgulamaktadır. Yeni ve nadir varyantların tanımlanması, Türk popülasyonundaki genetik çeşitliliği ortaya koymakta ve hasta yönetimi ile genetik danışmanlığın geliştirilmesi için genotip–fenotip haritalamasının sürdürülmesi gerektiğini göstermektedir.

Keywords

Marfan sendromu , FBN1 geni , Genotip-Fenotip Korelasyonu

Ethical Statement

Çalışmamız, Ordu Üniversitesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu’nun onayı ile yürütülmüştür (Karar No: 2025/308).

Supporting Institution

bu çalışmada herhangi bir kuruldan herhangi bir destek alınmamıştır

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