Genovesi Maria Luce, Torres Barbara, Goldoni Marina, Salvo Eliana, Cesario Claudia, Majolo Massimo, Mazza Tommaso, Piscopo Carmelo, Bernardini Laura
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Medical Genetics Division, IRCCS Casa Sollievo Della Sofferenza Foundation, San Giovanni Rotondo, Italy.
Front Genet. 2022 Jul 15;13:924362. doi: 10.3389/fgene.2022.924362. eCollection 2022.
Fibrillin proteins are extracellular matrix glycoproteins assembling into microfibrils. , , and encode the human fibrillins and mutations in and cause connective tissue disorders called fibrillinopathies, affecting cardiovascular, dermal, skeletal, and ocular tissues. Recently, mutations of the less characterized fibrillin family member, , 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 -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 (NM_032447:c.5434A>G; NP_115823:p.Ile1812Val; rs115948457), inherited from the heterozygous parents. This study further supports that 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.
原纤维蛋白是组装成微原纤维的细胞外基质糖蛋白。FBN1、FBN2和FBN3编码人类原纤维蛋白，FBN1和FBN2中的突变会导致称为原纤维蛋白病的结缔组织疾病，影响心血管、皮肤、骨骼和眼部组织。最近，特征较少的原纤维蛋白家族成员FBN3的突变在一个家族中与巴德-比德尔综合征（BBS）相关。在此，我们报告一名患者，其父母为近亲结婚，患有发育迟缓、认知障碍、肥胖、牙齿和生殖器异常以及短指/并指。他的表型与先前报道的FBN3突变家族非常相似，符合BBS临床诊断标准，尽管不像先前描述的兄弟姐妹那样具有最常见的临床特征——多指。对该唯一患者的纯合子区域进行了家族性单核苷酸多态性阵列分析和先证者的全外显子组测序，以优先筛选候选变异。该分析揭示了FBN3中的一个新的纯合错义变异（NM_032447:c.5434A>G；NP_115823:p.Ile1812Val；rs115948457），该变异从杂合子父母遗传而来。这项研究进一步支持FBN3是一种类似BBS综合征的候选基因，该综合征的特征为发育迟缓、认知障碍、肥胖、牙齿、生殖器和骨骼异常。无论如何，需要进一步研究来调查该基因的确切作用以及FBN3与BBS蛋白之间可能的相互作用。
