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Scientific Reports Jul 2023Branchio-oto-renal (BOR)/branchio-otic (BO) syndrome is a rare disorder and exhibits clinically heterogenous phenotypes, marked by abnormalities in the ear, branchial...
Branchio-oto-renal (BOR)/branchio-otic (BO) syndrome is a rare disorder and exhibits clinically heterogenous phenotypes, marked by abnormalities in the ear, branchial arch, and renal system. Sporadic cases of atypical BOR/BO syndrome have been recently reported; however, evidence on genotype-phenotype correlations and molecular mechanisms of those cases is lacking. We herein identified five SIX1 heterozygous variants (c.307dupC:p.Leu103Profs*51, c.373G>A:p.Glu125Lys, c.386_391del:p.Tyr129_Cys130del, c.397_399del:p.Glu133del, and c.501G>C:p.Gln167His), including three novel variants, through whole-exome sequencing in five unrelated Korean families. All eight affected individuals with SIX1 variants displayed non-syndromic hearing loss (DFNA23) or atypical BO syndrome. The prevalence of major and minor criteria for BOR/BO syndrome was significantly reduced among individuals with SIX1 variants, compared to 15 BOR/BO syndrome families with EYA1 variants. All SIX1 variants interacted with the EYA1 wild-type; their complexes were localized in the nucleus except for the p.Leu103Profs*51 variant. All mutants also showed obvious but varying degrees of reduction in DNA binding affinity, leading to a significant decrease in transcriptional activity. This study presents the first report of SIX1 variants in South Korea, expanding the genotypic and phenotypic spectrum of SIX1 variants, characterized by DFNA23 or atypical BO syndrome, and refines the diverse molecular aspects of SIX1 variants according to the EYA1-SIX1-DNA complex theory.
Topics: Humans; Intracellular Signaling Peptides and Proteins; Protein Tyrosine Phosphatases; Mutation; Pedigree; Branchio-Oto-Renal Syndrome; Phenotype; Republic of Korea; Deafness; DNA; Homeodomain Proteins
PubMed: 37479820
DOI: 10.1038/s41598-023-38909-w -
Intractable & Rare Diseases Research Feb 2018Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchial cleft fistulae or cysts, preauricular pits, ear malformations, hearing...
Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchial cleft fistulae or cysts, preauricular pits, ear malformations, hearing loss, and renal anomalies. Mutations in the human homologue of the Drosophila eyes absent gene () are the most common cause of BOR syndrome. PCR and direct sequencing were used to investigate all of the exons and exon-intron boundaries in the gene in a patient with BOR syndrome from China. The patient was a child who displayed clinical features of BOR syndrome. Analysis of mutations in the gene revealed a novel single base-pair deletion resulting in a truncated protein (c.1381delA; p.R461fs467X), and an analysis of mutations in the family revealed that this mutation was a mutation. This is the first case of BOR syndrome in mainland China to be diagnosed based on clinical manifestations and mutations in the gene. The novel c.1381delA mutation detected here expands the spectrum of known mutations in the gene.
PubMed: 29552445
DOI: 10.5582/irdr.2017.01075 -
BMJ Case Reports Aug 2012Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterised by branchial arch anomalies, otological and renal abnormalities. To the best of our...
Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterised by branchial arch anomalies, otological and renal abnormalities. To the best of our knowledge, upper airway obstruction has not been hitherto reported in BOR. The authors report a 19-month-old girl with BOR syndrome with features of severe airway obstruction needing tracheostomy.
Topics: Branchio-Oto-Renal Syndrome; Female; Humans; Infant; Pregnancy; Sleep Apnea, Obstructive; Tracheostomy; Ultrasonography, Prenatal
PubMed: 22891008
DOI: 10.1136/bcr.03.2009.1719 -
Journal of Dental Anesthesia and Pain... Sep 2017Branchio-oto-renal syndrome (BOR) is a rare autosomal dominant disorder. The features include branchial cysts, hearing loss, ear malformation, preauricular pits,...
Branchio-oto-renal syndrome (BOR) is a rare autosomal dominant disorder. The features include branchial cysts, hearing loss, ear malformation, preauricular pits, retrognathia, congenital heart disease, and renal abnormalities. However, anesthetic management of these patients has seldom been reported. We report a case in which general anesthesia was performed for dental treatment in a patient with BOR. Airway management, renal function, and hemodynamic changes can be of critical concern during anesthetic management. A 13-year-old girl diagnosed with BOR had severe right hearing loss, right external ear malformation, renal abnormalities, and postoperative patent ductus arteriosus (PDA). Dental extraction under general anesthesia was scheduled for a supernumerary tooth. The procedure was completed with sufficient urine volume, adequate airway management, and stable hemodynamics.
PubMed: 29090252
DOI: 10.17245/jdapm.2017.17.3.215 -
Italian Journal of Pediatrics Oct 2022Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by deafness, branchiogenic malformations and renal abnormalities. Pathogenic variants...
BACKGROUND
Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by deafness, branchiogenic malformations and renal abnormalities. Pathogenic variants in EYA1, SIX1 and SIX5 genes cause almost half of cases; copy number variants (CNV) and complex genomic rearrangements have been revealed in about 20% of patients, but they are not routinely and commonly included in the diagnostic work-up.
CASE PRESENTATION
We report two unrelated patients with BOR syndrome clinical features, negative sequencing for BOR genes and the identification of a 2.65 Mb 8q13.2-13.3 microdeletion.
CONCLUSIONS
We highlight the value of CNV analyses in high level of suspicion for BOR syndrome but negative sequencing for BOR genes and we propose an innovative diagnostic flow-chart to increase current detection rate. Our report confirms a mechanism of non-allelic homologous recombination as causing this recurrent 8q13.2-13.3 microdeletion. Moreover, considering the role of PRDM14 and NCOA2 genes, both involved in regulation of fertility and deleted in our patients, we suggest the necessity of a longer follow-up to monitor fertility issues or additional clinical findings.
Topics: Branchio-Oto-Renal Syndrome; Homeodomain Proteins; Humans; Intracellular Signaling Peptides and Proteins; Nuclear Proteins; Pedigree; Protein Tyrosine Phosphatases
PubMed: 36183088
DOI: 10.1186/s13052-022-01369-5 -
Molecular Genetics & Genomic Medicine Jul 2022Branchio-otic syndrome (BO) is one of the most common types of syndromic hearing impairment (HI) with an incidence of 1/40,000 globally. It is an autosomal dominant...
BACKGROUND
Branchio-otic syndrome (BO) is one of the most common types of syndromic hearing impairment (HI) with an incidence of 1/40,000 globally. It is an autosomal dominant disorder typically characterized by the coexistence of branchial cysts or fistulae, malformations of the external, middle, and inner ears with preauricular pits or tags and a variable degree of HI. Most cases of BO have been reported in populations of European ancestry. To date, only few cases have been reported in people from African descent.
METHODS
After a careful clinical examination, a pure tone audiometry was performed. DNA was extracted from peripheral blood and whole exome, and Sanger sequencing were performed for genetic analysis.
RESULTS
Eight individuals from a large non-consanguineous Malian family, with autosomal dominant inheritance were enrolled. The ages at diagnosis ranged from 8 to 54 years. A high phenotypic variability was noted among the affected individuals. Four patients presented with a post-lingual and mixed type of HI, one individual had conductive HI while three had normal hearing but presented other BO features namely branchial fistulae and preauricular sinus. Serum creatinine level and renal ultrasonography were normal in three affected individuals who performed them. Genetic testing identified a monoallelic pathogenic variant in EYA1 (c.1286A > G; p.Asp429Gly) segregating with BO syndrome in the family.
CONCLUSION
This is the first genetically confirmed case of BO syndrome caused by EYA1 variant in the sub-Saharan African population, expanding the genetic spectrum of the condition.
Topics: Adolescent; Adult; Branchio-Oto-Renal Syndrome; Child; Hearing Loss; Humans; Intracellular Signaling Peptides and Proteins; Middle Aged; Nuclear Proteins; Pedigree; Protein Tyrosine Phosphatases; Young Adult
PubMed: 35698919
DOI: 10.1002/mgg3.1995 -
Internal Medicine (Tokyo, Japan) Jul 2022Branchio-oto-renal syndrome is an autosomal dominant disorder characterized by branchial anomalies, hearing loss, and renal urinary tract malformations. We herein report...
Branchio-oto-renal syndrome is an autosomal dominant disorder characterized by branchial anomalies, hearing loss, and renal urinary tract malformations. We herein report a 32-year-old Japanese man with a right preauricular pit, bilateral mixed hearing loss, and malposition of the right kidney who presented with proteinuria. The findings of a left kidney biopsy were compatible with a perihilar variant of secondary focal segmental glomerular sclerosis. A trio exome analysis conducted among the patient and his parents failed to identify the causal gene variant, despite a sporadic pattern. His kidney function remained stable for 11 years with an angiotensin II receptor blocker.
Topics: Adult; Branchio-Oto-Renal Syndrome; Deafness; Glomerulosclerosis, Focal Segmental; Hearing Loss; Humans; Kidney; Male
PubMed: 34866102
DOI: 10.2169/internalmedicine.8508-21 -
Ugeskrift For Laeger Nov 2019This review describes congenital anomalies of the external ear, which are common and include a wide range of malformations. Attentiveness to other malformations in... (Review)
Review
This review describes congenital anomalies of the external ear, which are common and include a wide range of malformations. Attentiveness to other malformations in newborns with ear anomalies is important, as they often appear as part of syndromes such as Goldenhar syndrome, Treacher Collins syndrome and branchio-oto-renal syndrome. This review is an overview of the most common congenital anomalies of the external ear and their treatment, including microtia, constricted ears, preauricular pits, tags and prominent ears.
Topics: Branchio-Oto-Renal Syndrome; Ear, External; Humans; Infant, Newborn
PubMed: 31791458
DOI: No ID Found -
Neuro-ophthalmology (Aeolus Press) Dec 2017Renal osteodystrophy can cause calvarial hypertrophy and narrowing of the neural canals and foramina. Compressive optic neuropathy is extremely rare in renal...
Renal osteodystrophy can cause calvarial hypertrophy and narrowing of the neural canals and foramina. Compressive optic neuropathy is extremely rare in renal osteodystrophy and was reported once only. The authors report bilateral, simultaneous compressive optic neuropathy secondary to renal osteodystrophy with features of uremic leontiasis ossea in chronic renal failure caused by branchio-oto-renal syndrome. Because of the extensive calvarial hypertrophy and the surgical difficulties envisaged with optic canal decompression, conservative approach was pursued. The patient's visual acuity and fields improved after partial parathyroidectomy. Visual improvement may be explained by the arrest of renal osteodystrophy and reduced optic nerve compression after parathyroidectomy.
PubMed: 29344072
DOI: 10.1080/01658107.2017.1315145 -
BMC Nephrology Mar 2013Branchio-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...
BACKGROUND
Branchio-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 PRESENTATION
In 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.
CONCLUSION
This 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.
Topics: Adult; Branchio-Oto-Renal Syndrome; Glomerulosclerosis, Focal Segmental; Humans; Intracellular Signaling Peptides and Proteins; Male; Mutation; Nuclear Proteins; Protein Tyrosine Phosphatases; RNA Splice Sites
PubMed: 23506628
DOI: 10.1186/1471-2369-14-60