Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Genovesi, Maria Luce, Torres, Barbara, Goldoni, Marina, Salvo, Eliana, Cesario, Claudia, Majolo, Massimo, Mazza, Tommaso, Piscopo, Carmelo, Bernardini, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334770/
https://www.ncbi.nlm.nih.gov/pubmed/35910214
http://dx.doi.org/10.3389/fgene.2022.924362
_version_ 1784759178608246784
author Genovesi, Maria Luce
Torres, Barbara
Goldoni, Marina
Salvo, Eliana
Cesario, Claudia
Majolo, Massimo
Mazza, Tommaso
Piscopo, Carmelo
Bernardini, Laura
author_facet Genovesi, Maria Luce
Torres, Barbara
Goldoni, Marina
Salvo, Eliana
Cesario, Claudia
Majolo, Massimo
Mazza, Tommaso
Piscopo, Carmelo
Bernardini, Laura
author_sort Genovesi, Maria Luce
collection PubMed
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.
format Online
Article
Text
id pubmed-9334770
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-93347702022-07-30 Case Report: A Novel Homozygous Missense Variant of FBN3 Supporting It Is a New Candidate Gene Causative of a Bardet–Biedl Syndrome–Like Phenotype Genovesi, Maria Luce Torres, Barbara Goldoni, Marina Salvo, Eliana Cesario, Claudia Majolo, Massimo Mazza, Tommaso Piscopo, Carmelo Bernardini, Laura Front Genet Genetics 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. Frontiers Media S.A. 2022-07-15 /pmc/articles/PMC9334770/ /pubmed/35910214 http://dx.doi.org/10.3389/fgene.2022.924362 Text en Copyright © 2022 Genovesi, Torres, Goldoni, Salvo, Cesario, Majolo, Mazza, Piscopo and Bernardini. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Genovesi, Maria Luce
Torres, Barbara
Goldoni, Marina
Salvo, Eliana
Cesario, Claudia
Majolo, Massimo
Mazza, Tommaso
Piscopo, Carmelo
Bernardini, Laura
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 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 Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334770/
https://www.ncbi.nlm.nih.gov/pubmed/35910214
http://dx.doi.org/10.3389/fgene.2022.924362
work_keys_str_mv AT genovesimarialuce casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT torresbarbara casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT goldonimarina casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT salvoeliana casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT cesarioclaudia casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT majolomassimo casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT mazzatommaso casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT piscopocarmelo casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype
AT bernardinilaura casereportanovelhomozygousmissensevariantoffbn3supportingitisanewcandidategenecausativeofabardetbiedlsyndromelikephenotype