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A 45-year-old Italian male with p.(Gly1815Ser) FBN1 mutation causing a mild variant of Marfan syndrome: A case study
Francesca Cortini1, Chiara Villa2, Barbara Marinelli3, Sara Franchetti4, Luciano Riboldi5, Alessandra Bassotti4
1 Department of Clinical Sciences and Community Health, University of Milan, IRCCS Ca' Granda Foundation Via San Barnaba 8; UOC Occupational Medicine, Department of Medicine Preventive Services, IRCCS Ca' Granda Foundation Ospedale Maggiore Policlinico, via San Barnaba 8, Milan, Italy
2 Department of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, Monza, Italy
3 Department of Clinical Sciences and Community Health, University of Milan, IRCCS Ca' Granda Foundation Via San Barnaba 8, Milan, Italy
4 Regional Center of Ehlers-Danlos Syndrome, UOC Occupational Medicine, Department of Medicine Preventive Services, IRCCS Ca' Granda Foundation Ospedale Maggiore Policlinico, via San Barnaba 8, Milan, Italy
5 UOC Occupational Medicine, Department of Medicine Preventive Services, IRCCS Ca' Granda Foundation Ospedale Maggiore Policlinico, via San Barnaba 8, Milan, Italy
Correspondence Address:
Dr. Francesca Cortini
Department of Clinical Sciences and Community Health, University of Milan, Via San Barnaba 8, 20122, Milan
Italy
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ds.ds_16_19
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A 45-year-old Italian male was referred as suspected of having a heritable connective tissue disorders by clinical findings, including joint hyperlaxity and soft, smooth, velvety, and slightly elastic skin. Using a specific custom panel including genes involved in these disorders, next-generation sequencing (NGS) analysis led to the identification of the c. 5443G>A, p.(Gly1815Ser), (rs745680336) variant in fibrillin-1 (FBN1) gene, encoding the FBN1. Mutations in this protein are responsible for different connective tissue disorders, collectively known as type 1 fibrillinopathies, including Marfan syndrome (MFS). Multiple sequencing alignment of human FBN1 protein with various species revealed that the mutation occurred within a highly conserved region of the calcium-binding epidermal growth factor-like domain and affected the protein structure/function, suggesting its pathogenic role. NGS techniques successfully identified the molecular defect in this patient, clinically resembling as MFS, even if a clear genotype–phenotype correlation remains still challenging.
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