Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype
Fibrillin proteins are extracellular matrix glycoproteins assembling into microfibrils. FBN1, FBN2, and FBN3 encode the human fibrillins and mutations in FBN1 and FBN2 cause connective tissue disorders called fibrillinopathies, affecting cardiovascular, dermal, skeletal, and ocular tissues. Recently...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.924362/full |
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| author | Maria Luce Genovesi Barbara Torres Marina Goldoni Eliana Salvo Claudia Cesario Massimo Majolo Tommaso Mazza Carmelo Piscopo Laura Bernardini |
| author_facet | Maria Luce Genovesi Barbara Torres Marina Goldoni Eliana Salvo Claudia Cesario Massimo Majolo Tommaso Mazza Carmelo Piscopo Laura Bernardini |
| author_sort | Maria Luce Genovesi |
| collection | DOAJ |
| description | Fibrillin proteins are extracellular matrix glycoproteins assembling into microfibrils. FBN1, FBN2, and FBN3 encode the human fibrillins and mutations in FBN1 and FBN2 cause connective tissue disorders called fibrillinopathies, affecting cardiovascular, dermal, skeletal, and ocular tissues. Recently, mutations of the less characterized fibrillin family member, FBN3, have been associated in a single family with Bardet–Biedl syndrome (BBS). Here, we report on a patient born from two first cousins and affected by developmental delay, cognitive impairment, obesity, dental and genital anomalies, and brachydactyly/syndactyly. His phenotype was very similar to that reported in the previous FBN3-mutated family and fulfilled BBS clinical diagnostic criteria, although lacking polydactyly, the most recurrent clinical feature, as the previous siblings described. A familial SNP-array and proband’s WES were performed prioritizing candidate variants on the sole patient’s runs of homozygosity. This analysis disclosed a novel homozygous missense variant in FBN3 (NM_032447:c.5434A>G; NP_115823:p.Ile1812Val; rs115948457), inherited from the heterozygous parents. This study further supports that FBN3 is a candidate gene for a BBS-like syndrome characterized by developmental delay, cognitive impairment, obesity, dental, genital, and skeletal anomalies. Anyway, additional studies are necessary to investigate the exact role of the gene and possible interactions between FBN3 and BBS proteins. |
| first_indexed | 2024-12-11T16:58:01Z |
| format | Article |
| id | doaj.art-9f76a4111751483788812d8a8a0d5c14 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T16:58:01Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-9f76a4111751483788812d8a8a0d5c142022-12-22T00:57:54ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-07-011310.3389/fgene.2022.924362924362Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like PhenotypeMaria Luce Genovesi0Barbara Torres1Marina Goldoni2Eliana Salvo3Claudia Cesario4Massimo Majolo5Tommaso Mazza6Carmelo Piscopo7Laura Bernardini8Department of Experimental Medicine, Sapienza University of Rome, Rome, ItalyMedical Genetics Division, IRCCS Casa Sollievo Della Sofferenza Foundation, San Giovanni Rotondo, ItalyMedical Genetics Division, IRCCS Casa Sollievo Della Sofferenza Foundation, San Giovanni Rotondo, ItalyMedical Genetics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, ItalyTranslational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyHospital Directorate, National Hospital A.O.R.N. “Antonio Cardarelli”, Naples, ItalyLaboratory of Bioinformatics, IRCCs Casa Sollievo Della Sofferenza Foundation, San Giovanni Rotondo, ItalyMedical and Laboratory Genetics Unit, National Hospital A.O.R.N. “Antonio Cardarelli”, Naples, ItalyMedical Genetics Division, IRCCS Casa Sollievo Della Sofferenza Foundation, San Giovanni Rotondo, ItalyFibrillin proteins are extracellular matrix glycoproteins assembling into microfibrils. FBN1, FBN2, and FBN3 encode the human fibrillins and mutations in FBN1 and FBN2 cause connective tissue disorders called fibrillinopathies, affecting cardiovascular, dermal, skeletal, and ocular tissues. Recently, mutations of the less characterized fibrillin family member, FBN3, have been associated in a single family with Bardet–Biedl syndrome (BBS). Here, we report on a patient born from two first cousins and affected by developmental delay, cognitive impairment, obesity, dental and genital anomalies, and brachydactyly/syndactyly. His phenotype was very similar to that reported in the previous FBN3-mutated family and fulfilled BBS clinical diagnostic criteria, although lacking polydactyly, the most recurrent clinical feature, as the previous siblings described. A familial SNP-array and proband’s WES were performed prioritizing candidate variants on the sole patient’s runs of homozygosity. This analysis disclosed a novel homozygous missense variant in FBN3 (NM_032447:c.5434A>G; NP_115823:p.Ile1812Val; rs115948457), inherited from the heterozygous parents. This study further supports that FBN3 is a candidate gene for a BBS-like syndrome characterized by developmental delay, cognitive impairment, obesity, dental, genital, and skeletal anomalies. Anyway, additional studies are necessary to investigate the exact role of the gene and possible interactions between FBN3 and BBS proteins.https://www.frontiersin.org/articles/10.3389/fgene.2022.924362/fullBardet–Biedl syndromeFBN3fibrillinopathiesSNP-arraywhole-exome sequencing |
| spellingShingle | Maria Luce Genovesi Barbara Torres Marina Goldoni Eliana Salvo Claudia Cesario Massimo Majolo Tommaso Mazza Carmelo Piscopo Laura Bernardini Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype Frontiers in Genetics Bardet–Biedl syndrome FBN3 fibrillinopathies SNP-array whole-exome sequencing |
| title | Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype |
| title_full | Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype |
| title_fullStr | Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype |
| title_full_unstemmed | Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype |
| title_short | Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype |
| title_sort | case report a novel homozygous missense variant of fbn3 supporting it is a new candidate gene causative of a bardet biedl syndrome like phenotype |
| topic | Bardet–Biedl syndrome FBN3 fibrillinopathies SNP-array whole-exome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.924362/full |
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