المؤلفون: Hui Zhang, Jian Gao, Hanjun Wang, Mengli Liu, Shuangshuang Lu, Hongen Xu, Wenxue Tang, Guoxi Zheng

المصدر: BMC Medical Genomics, Vol 17, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: EYA1 gene, Branchio-oto-renal syndrome, Whole-exome sequencing, Internal medicine, RC31-1245, Genetics, QH426-470

الوصف: Abstract Objective Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms. Methods The family spans 4 generations and consists of 9 individuals, including 4 affected by the BOR/BO syndrome. Phenotypic information, including ear malformation and branchial cleft, was collected from family members. Audiological, temporal bone imaging, and renal ultrasound examinations were also performed. Whole-exome sequencing was conducted to identify candidate pathogenic variants and explore the underlying molecular etiology of BOR/BO syndrome by minigene experiments. Results Intra-familial variability was observed in the clinical phenotypes of BOR/BO syndrome in this family. The severity and nature of hearing loss varied in family members, with mixed or sensorineural hearing loss. The proband, in particular, had profound sensorineural hearing loss on the left and moderate conductive hearing loss on the right. Additionally, the proband exhibited developmental delay, and her mother experienced renal failure during pregnancy and terminated the pregnancy prematurely. Genetic testing revealed a novel heterozygous variant NM_000503.6: c.639 + 3 A > C in the EYA1 gene in affected family members. In vitro minigene experiments demonstrated its effect on splicing. According to the American College of Medical Genetics (ACMG) guidelines, this variant was classified as likely pathogenic. Conclusion This study highlights the phenotypic heterogeneity within the same family, reports the occurrence of renal failure and adverse pregnancy outcomes in a female patient at reproductive age with BOR syndrome, and enriches the mutational spectrum of pathogenic variants in the EYA1 gene.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1755-8794Test

الوصول الحر: https://doaj.org/article/3af2a963f61941838169b602feab7d12Test

المؤلفون: Zhilang Lin, Jie Li, Yuxin Pei, Ying Mo, Xiaoyun Jiang, Lizhi Chen

المصدر: BMC Nephrology, Vol 24, Iss 1, Pp 1-7 (2023)

مصطلحات موضوعية: Branchio-oto-renal syndrome, Proteinuria, Renal insufficiency, Kidney failure, Genetic testing, Immune complex-mediated glomerulonephritis, Diseases of the genitourinary system. Urology, RC870-923

الوصف: Abstract Background Branchio-oto-renal (BOR) syndrome is an inherited multi-systemic disorder. Auricular and branchial signs are highly suggestive of BOR syndrome but often develop insidiously, leading to a remarkable misdiagnosis rate. Unlike severe morphological abnormalities of kidneys, knowledge of glomerular involvement in BOR syndrome were limited. Case presentation Three cases, aged 8 ~ 9 years, visited pediatric nephrology department mainly for proteinuria and renal insufficiency, with 24-h proteinuria of 23.8 ~ 68.9 mg/kg and estimated glomerular filtration rate of 8.9 ~ 36.0 mL/min/1.73m2. Moderate-to-severe albuminuria was detected in case 1, while mixed proteinuria was detected in case 2 and 3. Insidious auricular and branchial fistulas were noticed, all developing since early childhood but being neglected previously. EYA1 variants were confirmed by genetic testing in all cases. Delay in diagnosis was 8 ~ 9 years since extra-renal appearances, and 0 ~ 6 years since renal abnormalities. In case 1, therapy of glucocorticoid and immunosuppressive agents to accompanying immune-complex mediated glomerulonephritis was unsatisfying. Conclusions BOR syndrome is a rare cause of proteinuria and abnormal kidney function and easily missed, thus requiring more awareness. Careful medical history taking and physical examination are essential to early diagnosis. Massive proteinuria was occasionally seen in BOR syndrome, which might be related to immune complex deposits. A novel pathogenic variant (NM_000503.6 (EYA1): c.1171delT p.Ser391fs*9) was firstly reported.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2369Test

الوصول الحر: https://doaj.org/article/cf80374fca9e494b82d3309579ea4303Test

المؤلفون: Luciano A. Favorito, Marcio Luiz P. Lobo, Ana Vitória Fernandes, Carla M. Gallo, Francisco J. B. Sampaio

المصدر: International Brazilian Journal of Urology, Vol 48, Iss 6, Pp 930-936 (2022)

مصطلحات موضوعية: Kidney, Branchio-Oto-Renal Syndrome, Embryology, Diseases of the genitourinary system. Urology, RC870-923

الوصف: ABSTRACT Objective: To evaluate the anatomical aspects of the kidney surface in human fetuses during the second gestational trimester. Material and Methods: We studied 108 kidneys obtained from 54 human fetuses (29 males and 25 females). The kidney was dissected and the number of clefts was counted. The renal volume was also assessed. To compare the quantitative data in both sexes, the Students-t-test was used (p < 0.05). Simple linear correlations were calculated for all kidney measurements, according to fetal age. Statistical analysis was performed with the R program (Version 3.5.1). Results: The fetuses ranged in age between 11.4 to 23 weeks post-conception. The renal volume of the right kidney ranged from 0.09 to 2.397 cm (mean=0.8479) and the renal volume of the left kidney ranged from 0.07 to 2.416 cm (mean=0.8036). The mean number of renal clefts in fetuses studied was 15.25 (7 to 28). There was no statistical significant difference in renal clefts between the sides either in males (p = 0.646) or in females (p = 0.698). Also, there was no significant difference in the mean number of renal clefts between male and female fetuses in right kidney (p = 0.948) and in left kidney (p = 0.939). Conclusions: The number of renal clefts has a great variation, weak correlation and no tendency to decrease during the 2nd gestational trimester. The number of clefts in right kidney of total sample and female fetuses has a significant development with age.

وصف الملف: electronic resource

العلاقة: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1677-55382022000600930&tlng=enTest; https://doaj.org/toc/1677-6119Test

الوصول الحر: https://doaj.org/article/869d1bf0d27f40038ca4da919a6aa365Test

المؤلفون: Dandan Liu, Yafeng Wang

المصدر: BMC Pediatrics, Vol 22, Iss 1, Pp 1-5 (2022)

مصطلحات موضوعية: Branchio-Oto-Renal syndrome, Infants, Congenital heart defects, Proteinuria, Genetic sequencing analysis, Case report, Pediatrics, RJ1-570

الوصف: Abstract Background Branchio-Oto-Renal (BOR) Syndrome is a rare autosomal disorder with a wide variety of clinical manifestations and a high degree of heterogeneity. Typical clinical manifestations of BOR syndrome include deafness, preauricular fistula, abnormal gill slits, and renal malformations. However, atypical phenotypes such as congenital hip dysplasia, congenital heart anomaly or facial nerve paresis are rare in BOR syndrome, and this might be easily misdiagnosed with other congenital disorders. Case presentation We report a 5-month-old boy of BOR syndrome with "congenital heart defects and proteinuria" as clinical features. Initially, as this case mainly presented with symptoms of recurrent respiratory infections and was found to be with congenital heart disease and proteinuria at the local hospital, but he only was diagnosed with congenital heart disease combined with pulmonary infection and anti-infective and supportive treatment was given. Subsequently, during the physical examination at our hospital, left side preauricular pit and branchial fistulae on the right neck were found. Subsequent evaluation of auditory brainstem response and distortion product otoacoustic emission were revealed sensorineural hearing impairment. Results of renal ultrasonography showed small kidneys. Genetic analysis revealed a microdeletion at chromosome 8q13.2-q13.3 encompassing EYA1 gene, this patient was finally diagnosed with BOR syndrome. Then, this patient received transcatheter patent ductus arteriosus closure and hearing aid treatment. Proteinuria, renal function and hearing ability are monitoring by nephrologist and otologist. The patient is currently being followed up until 3 months after discharge and his condition is stable. Conclusion Careful physical examination, detailed history and the implementation of diagnostic laboratory tests can reduce the incidence of misdiagnosis. Genetic sequencing analysis of patients is a key guide to the differential diagnosis of BOR syndrome.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2431Test

الوصول الحر: https://doaj.org/article/eb3a816d19924b0e9f00d0ffe783450aTest

المؤلفون: Elena Cacciatori, Sebastiano Aleo, Giulietta Scuvera, Chiara Rigon, Paola Giovanna Marchisio, Matteo Cassina, Donatella Milani

المصدر: Italian Journal of Pediatrics, Vol 48, Iss 1, Pp 1-6 (2022)

مصطلحات موضوعية: Branchio-oto-renal syndrome, Deafness, EYA1, Copy number variation – case report, Pediatrics, RJ1-570

الوصف: Abstract 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.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1824-7288Test

الوصول الحر: https://doaj.org/article/8030015ccf53465ba0ce88cd1561ec68Test

المؤلفون: Kim, Da Hyeon, Yang, Misun, Jo, Heui Seung, Park, JongHo, Jang, JaHyun, Shin, Sunghwan, Son, SeHyung

المصدر: Children; Jan2023, Vol. 10 Issue 1, p76, 10p

مصطلحات موضوعية: NECK surgery, BICORNUATE uterus, PREMATURE infants, SEQUENCE analysis, NEONATAL intensive care, GENETIC mutation, DEGLUTITION, RESPIRATORY aspiration, NEONATAL diseases, HUMAN genome, GENETIC polymorphisms, VERY low birth weight, NEONATAL intensive care units, POSTOPERATIVE care, INFANT nutrition, BRANCHIO-oto-renal syndrome, GENES, BARIUM, DYES & dyeing, CYANOSIS, CESAREAN section, EARLY diagnosis, DISEASE complications

مصطلحات جغرافية: SOUTH Korea

مستخلص: Branchiootorenal (BOR) syndrome is a rare autosomal dominant inherited disease with a prevalence of approximately 1 in 40,000 newborns. This disease is characterized by hearing loss, preauricular pits, branchial fistulas or cysts, and renal dysplasia. We discovered a case of BOR syndrome in a premature 2-week-old female infant with a gestational age of 32 weeks and two days. She and her family had major symptoms and a family history of BOR. BOR syndrome was confirmed by whole-genome sequencing and structural variant calling, which revealed an EYA1 exon 5–6 deletion. The infant had recurrent sleep and feeding cyanosis with second branchial anomalies. Via videofluoroscopic swallowing study and a modified barium swallow test, penetration into the vocal cords was observed before and during swallowing when bottle feeding. This is the first report of a preterm infant early diagnosed with BOR syndrome in which deletion margin was accurately identified by whole-genome sequencing and structural variant calling in Republic of Korea. [ABSTRACT FROM AUTHOR]

: Copyright of Children is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Cacciatori, Elena, Aleo, Sebastiano, Scuvera, Giulietta, Rigon, Chiara, Marchisio, Paola Giovanna, Cassina, Matteo, Milani, Donatella

المصدر: Italian Journal of Pediatrics; 10/1/2022, Vol. 48 Issue 1, p1-6, 6p

مصطلحات موضوعية: MOLECULAR diagnosis, SEQUENCE analysis, DEAFNESS, GENETIC polymorphisms, BRANCHIO-oto-renal syndrome, CHROMOSOME abnormalities

مستخلص: 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. [ABSTRACT FROM AUTHOR]

: Copyright of Italian Journal of Pediatrics is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Juan M. Fons, Natalie J. Milmoe, Michael R. G. Dack, Leena Joshi, Hannah Thompson, Abigail S. Tucker

المصدر: Frontiers in Genetics, Vol 13 (2022)

مصطلحات موضوعية: ear development, congenital birth defect, branchio-oto-renal syndrome, cavitation, basal cell hyperplasia, Genetics, QH426-470

الوصف: High incidence of chronic otitis media is associated with human craniofacial syndromes, suggesting that defects in the formation of the middle ear and associated structures can have a knock-on effect on the susceptibility to middle ear inflammation. Patients with branchio-oto-renal (BOR) syndrome have several defects in the ear leading to both sensorineural and conductive hearing loss, including otitis media. 40% of BOR syndrome cases are due to Eya1 haploinsufficiency, with mouse models affecting Eya1, mimicking many of the defects found in patients. Here, we characterize the onset, consequences, and underlying causes of chronic otitis media in Eya1 heterozygous mice. Cavitation defects were evident in these mice from postnatal day (P)11 onwards, with mesenchyme around the promontory and attic regions of the middle ear space. This mesenchyme was still prominent in adult Eya1 heterozygous mice, while the wild-type littermates had fully aerated ears from P14 onwards. MicroCT analysis highlighted a significantly smaller bulla, confirming the link between bulla size defects and the ability of the mesenchyme to retract successfully. Otitis media was observed from P14, often presenting unilaterally, resulting in hyperplasia of the middle ear mucosa, expansion of secretory cells, defects in the motile cilia, and changes in basal epithelial cell markers. A high incidence of otitis media was identified in older mice but only associated with ears with retained mesenchyme. To understand the impact of the environment, the mouse line was rederived onto a super-clean environment. Cavitation defects were still evident at early stages, but these generally resolved over time, and importantly, no signs of otitis media were observed at 6 weeks. In conclusion, we show that a small bulla size is closely linked to defects in cavitation and the presence of retained mesenchyme. A delay in retraction of the mesenchyme predates the onset of otitis media, making the ears susceptible to its development. Early exposure to OM appears to exacerbate the cavitation defect, with mesenchyme evident in the middle ear throughout the animal’s life. This highlights that permanent damage to the middle ear can arise as a consequence of the early onset of OM.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fgene.2022.933416/fullTest; https://doaj.org/toc/1664-8021Test

الوصول الحر: https://doaj.org/article/8436aff2f2804f2885274fbbdd245d02Test

المؤلفون: Shen, Li-Fang¹ 11418276@zju.edu.cn, Zhou, Shui-Hong¹ 1190051@zju.edu.cn, Chen, Qiong-qiong¹, Yu, Qi¹

المصدر: Pediatric Surgery International. Dec2018, Vol. 34 Issue 12, p1251-1256. 6p. 1 Color Photograph.

مصطلحات موضوعية: *BRANCHIAL cleft fistula, *BRANCHIO-oto-renal syndrome, *HUMAN abnormalities, *CHILDREN, *ENDOSCOPIC surgery

مستخلص: Branchial cleft anomalies are the second most common head and neck congenital lesions in children. It may sometimes be a part of branchio-oto-renal (BOR) syndrome, so in patients with branchial cleft anomalies associated with a complaint of auricular deformity or a similar history and findings in other family members, we should take an additional examination to find the possibility of BOR syndrome. Complete excision is essential for good prognosis. For the management of branchial cleft anomalies, various methods have been reported. Endoscopically assisted dissection technique and transoral robot-assisted surgery were used in the management of fistula and allowed excellent visualization of the pharyngeal component of the lesion and a minimally invasive approach. It is essential for the surgeon to fully comprehend the congenital lesions to attain the correct preoperative diagnosis and plan for an appropriate surgical approach to prevent the most common complication and recurrence in these lesions. The following sections discuss the anatomy, common presentation, auxiliary examination, differential diagnosis, the current principles of surgical treatment and prognosis for second branchial cleft anomalies in children, and discussed the branchio-oto-renal syndrome. [ABSTRACT FROM AUTHOR]

المؤلفون: Parkes, William J.^1,2 william.parkes@nemours.org, Cushing, Sharon L.³, Blaser, Susan I.^3,4, Papsin, Blake C.³

المصدر: International Journal of Pediatric Otorhinolaryngology. Nov2018, Vol. 114, p92-96. 5p.

مصطلحات موضوعية: *BRANCHIO-oto-renal syndrome, *MASTOID process surgery, *COCHLEAR implants, *COMPUTED tomography

مستخلص: Abstract Objective To evaluate for temporal bone abnormalities that might affect transmastoid surgery such as cochlear implantation in cases of branchio-oto-renal syndrome (BOR). Study design Retrospective review. Methods Qualitative assessment of temporal bone computed tomography imaging was performed by a neuroradiologist for 30 individuals with BOR (60 ears) and 20 controls with normal hearing (20 ears). Transmastoid access was assessed categorically across 4 features: tip development, cortex pneumatization, tegmen height, and facial recess pneumatization. The appearance of 4 standard landmarks (Koerner's septum, antrum, prominence of the horizontal semicircular canal, incudal short process) was also dichotomized as normal or abnormal. Data were compared using Fisher's exact testing. Results Mastoid height differed between the groups with tip underdevelopment noted in 72% of BOR ears vs. 40% of controls (p = 0.02), and a low tegmen was seen in 68% of BOR ears and 25% of controls (p < 0.01). Significant differences in pneumatization were also found for the mastoid cortex (28% non-pneumatized in BOR vs. 5% in controls; p = 0.03) and the facial recess (27% non-pneumatized in BOR vs. 0% in controls; p = 0.01). Standard landmarks were easily identified in all of the control mastoids. In the BOR group, Koerner's septum was abnormally located or absent in 45%, and the antrum was severely hypoplastic or absent in 50%. Similarly, the prominence of the horizontal semicircular canal and the short process of the incus were dysplastic in 73% (44/60) and 62% (37/60), respectively. Conclusions Mastoid abnormalities are common in BOR syndrome. Restricted transmastoid access and abnormal or absent mastoid landmarks should be anticipated in those patients with BOR who become cochlear implant candidates. Level of evidence 4. [ABSTRACT FROM AUTHOR]