Branchio-Oto-Renal Syndrome (BOR) associated with focal glomerulosclerosis in a patient with a novel EYA1 splice site mutation

Abstract

BackgroundBranchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by branchial, ear, and renal anomalies. The most common gene mutated in BOR patients is EYA1, the human homolog of the Drosophila eyes absent gene, while mutations in SIX1 gene, the human homolog of sine oculis, encoding a DNA binding protein interacting with EYA1, have been reported less frequently. Recently, mutations in another SIX family member, SIX5, have been described in BOR patients, however, this association has not been confirmed by other groups.Case presentationIn this study, we have clinically and genetically characterized a proband that displayed hearing loss, pre-auricular pits, branchial fistulae, hypoplasia of the left kidney, bilateral mild hydronephrosis, progressive proteinuria and focal glomerulosclerosis. Mutational analysis of EYA1 gene revealed a novel splice site mutation, c.1475 + 1G > C, that affects EYA1 splicing and produces an aberrant mRNA transcript, lacking exon 15, which is predicted to encode a truncated protein of 456 aa.ConclusionThis report provided the functional description of a novel EYA1 splice site mutation and described for the first time a case of BOR syndrome associated with the atypical renal finding of focal glomerulosclerosis, highlighting the importance of molecular testing and detailed clinical evaluation to provide accurate diagnosis and appropriate genetic counselling.

Branchio‐oto‐renal syndrome: Comprehensive review based on nationwide surveillance in Japan

“…Gigante et al . reported an adult male patient with a BOR phenotype resulting from an EYA1 mutation who presented with focal segmental glomerulosclerosis . In the present study, a patient with BOR syndrome presented with membranous nephropathy resulting from an EYA1 partial deletion.…”

PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma

“…PTX-3 serum levels were tested on serum samples drawn at the time of nephrectomy in the whole study population. Circulating PTX3 was measured was assayed using a commercially available ELISA Kit, according to the manufacturer's instructions (R&D Systems, Minneapolis, MN), as previously described [66,67].…”

Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem

“…FSGS can be idiopathic, secondary and reactive, or poorly adapted. The primary form includes all those in which the cause is unknown; the secondary form includes a variety of etiologies, such as genetic, viral (e.g., HIV, parvovirus B19, cytomegalovirus, EBV), drug-induced (e.g., heroin, lithium, interferon, calcineurin inhibitors); the reactive form represents the final histological lesions that are common to any progressive renal damage [ 86 , 87 ]. Typically, only primary FSGS recurs after renal transplantation [ 88 ].…”