HERV‐mediated genomic rearrangement of EYA1 in an individual with branchio‐oto‐renal syndrome
Open accessAbstract
Branchio‐oto‐renal syndrome is characterized by branchial defects, hearing loss, preauricular pits, and renal anomalies. Mutations in EYA1 are the most common cause of branchio‐oto‐renal and branchio‐otic syndromes. Large chromosomal aberrations of 8q13, including complex rearrangements occur in about 20% of these individuals. However, submicroscopic deletions and the molecular characterization of genomic rearrangements involving the EYA1 gene have rarely been reported. Using the array‐comparative genomic hybridization, we identified non‐recurrent genomic deletions including the EYA1 gene in three patients with branchio‐oto‐renal syndrome, short stature, and developmental delay. One of these deletions was mediated by two human endogenous retroviral sequence blocks, analogous to the AZFa microdeletion on Yq11, responsible for male infertility. This report describes the expanded phenotype of individuals, resulting from contiguous gene deletion involving the EYA1 gene and provides a molecular description of the genomic rearrangements involving this gene in branchio‐oto‐renal syndrome. © 2010 Wiley‐Liss, Inc.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Loss of the eyes absent 1 (EYA1) gene in branchio-oto-renal syndrome and recurrent unbalanced translocations leading to intellectual disability result from recombination between HERV-H copies.
“Also, loss of the eyes absent 1 (EYA1) gene in branchio-oto-renal syndrome and recurrent unbalanced translocations leading to intellectual disability have been shown to result from recombination between HERV-H copies 23,24.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [24]
The Results (Patient 1; page not specified) and Discussion describe an EYA1 deletion in branchio-oto-renal syndrome, with recombination between LTR/ERV1 elements as the likely mechanism. They do not identify HERV-H copies or report recurrent unbalanced translocations leading to intellectual disability; the Discussion explicitly calls the deletions in this series non-recurrent. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia
Xu, P., Adams, J. C., Peters, H., Brown, M. C., Heaney, S., & Maas, R. L. (1999) · Nature Genetics · doi:10.1038/12722 · Cited by 725 · see citing works
Abdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samson, D. S., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M., et al. (1997) · Nature Genetics · doi:10.1038/ng0297-157 · Cited by 669 · see citing works
Bonini, N. M., Leiserson, W. M., & Benzer, S. (1993) · Cell · doi:10.1016/0092-8674(93)90115-7 · Cited by 559 · see citing works
SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1–SIX1–DNA complexes
Ruf, R. G., Xu, P., Silvius, D., Otto, E. A., Beekmann, F., Schultheiß, U. T., Kumar, S., Neuhaus, T. J., Kemper, M. J., Raymond, R. M., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308475101 · Cited by 425 · see citing works
Fluorescence in situ hybridization: applications in cytogenetics and gene mapping
Trask, B. J. (1991) · Trends in Genetics · doi:10.1016/0168-9525(91)90378-4 · Cited by 415 · see citing works
Branchio-oto-renal syndrome: The mutation spectrum in EYA1 and its phenotypic consequences
Chang, E. H., Menezes, M. D., Meyer, N. C., Cucci, R. A., Vervoort, V. S., Schwartz, C. E., & Smith, R. J. (2004) · Human Mutation · doi:10.1002/humu.20048 · Cited by 226 · see citing works
Kamp, C. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.17.2563 · Cited by 222 · see citing works
Transcription Factor SIX5 Is Mutated in Patients with Branchio-Oto-Renal Syndrome
Hoskins, B. E., Cramer, C. H., Silvius, D., Zou, D., Raymond, R. M., Orten, D. J., Kimberling, W. J., Smith, R. J., Weil, D., Petit, C., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/513322 · Cited by 200 · see citing works
Familial branchio‐oto‐renal dysplasia: A new addition to the branchial arch syndromes
Melnick, M., Bixler, D., Nance, W. E., Silk, K. R., & Yune, H. (1976) · Clinical Genetics · doi:10.1111/j.1399-0004.1976.tb01546.x · Cited by 173 · see citing works
Endogenous retroviruses and the human germline
Bock, M., & Stoye, J. P. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00138-6 · Cited by 128 · see citing works
Fan, Y., Jayakar, P., Zhu, H., Barbouth, D., Sacharow, S. J., Morales, A., Carver, V. H., Benke, P. J., Mundy, P. C., & Elsas, L. J. (2007) · Human Mutation · doi:10.1002/humu.20581 · Cited by 126 · see citing works
Vincent, C., Kalatzis, V., Compain, S., Levilliers, J., Slim, R., Graïa, F., Pereira, M. L., Nivelon, A., Croquette, M. F., Lacombe, D., et al. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.10.1859 · Cited by 119 · see citing works
Heimler, A., Lieber, E., Opitz, J. M., & Reynolds, J. F. (1986) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320250104 · Cited by 119 · see citing works
Kochhar, A., Orten, D. J., Sorensen, J. L., Fischer, S. M., Cremers, C. W. R. J., Kimberling, W. J., & Smith, R. J. (2008) · Human Mutation · doi:10.1002/humu.20714 · Cited by 95 · see citing works
Zou, D., Silvius, D., Rodrigo-Blomqvist, S., Enerbäck, S., & Xu, P. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.06.049 · Cited by 92 · see citing works
Ou, Z., Kang, S.-H. L., Shaw, C. A., Carmack, C. E., White, L. D., Patel, A., Beaudet, A. L., Cheung, S. W., & Chinault, A. C. (2008) · Genetics in Medicine · doi:10.1097/gim.0b013e31816b4420 · Cited by 90 · see citing works
Self-citationRetroelements in the human MHC class II region
Andersson, G., Svensson, A.-C., Setterblad, N., & Rask, L. (1998) · Trends in Genetics · doi:10.1016/s0168-9525(97)01359-0 · Cited by 89 · see citing works
Haan, E., Hull, Y., White, S., COCKINGTON, R. A., Charlton, P., & Callen, D. F. (1989) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320320412 · Cited by 68 · see citing works
Rickard, S. J., Hoff, W. V., Barnicoat, A. J., Russell‐Eggitt, I., Winter, R. M., Bitner-Glindzicz, M. A. K., & Parker, M. J. (2001) · Human Genetics · doi:10.1007/s004390100495 · Cited by 64 · see citing works
Genomic rearrangements of EYA1 account for a large fraction of families with BOR syndrome
Vervoort, V. S., Smith, R. J. H., O'Brien, J., Schroer, R. J., Abbott, A. G., Stevenson, R. E., & Schwartz, C. E. (2002) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200877 · Cited by 51 · see citing works
Point Mutation of an EYA1‐gene Splice Site in a Patient with Oto‐facio‐cervical Syndrome
Estefanía, E., Ramírez‐Camacho, R., Gomar, M., Trinidad, A., Arellano, B., García‐Berrocal, J. R., Verdaguer, J. M., & Vilches, C. (2005) · Annals of Human Genetics · doi:10.1111/j.1529-8817.2005.00204.x · Cited by 30 · see citing works
Kulski, J. K., Anzai, T., & Inoko, H. (2005) · Cytogenetic and Genome Research · doi:10.1159/000084951 · Cited by 22 · see citing works
Gu, J. Z., Wagner, M. J., Haan, E., & Wells, D. E. (1996) · Genomics · doi:10.1006/geno.1996.0032 · Cited by 15 · see citing works
Patient with an EYA1 mutation with features of branchio-oto-renal and oto-facio-cervical syndrome
Mercer, C., Gilbert, R. D., Loughlin, S., & Foulds, N. C. (2006) · Clinical Dysmorphology · doi:10.1097/01.mcd.0000204986.54366.7c · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Endogenous viruses: insights into viral evolution and impact on host biology
Feschotte, C., & Gilbert, C. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3199 · Cited by 885 · see citing works
Parental Somatic Mosaicism Is Underrecognized and Influences Recurrence Risk of Genomic Disorders
Campbell, I. M., Yuan, B., Robberecht, C., Pfundt, R., Szafrański, P., McEntagart, M., Nagamani, S. C. S., Erez, A., Bartnik, M., Wiśniowiecka‐Kowalnik, B., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.07.003 · Cited by 274 · see citing works
Self-citationDetection of clinically relevant exonic copy-number changes by array CGH
Boone, P. M., Bacino, C. A., Shaw, C. A., Eng, P. A., Hixson, P. M., Pursley, A. N., Kang, S.-H. L., Yang, Y., Wiszniewska, J., Nowakowska, B., et al. (2010) · Human Mutation · doi:10.1002/humu.21360 · Cited by 238 · see citing works
Self-citationNeurocristopathies: New insights 150 years after the neural crest discovery
Vega‐López, G. A., Cerrizuela, S., Tríbulo, C., & Aybar, M. J. (2018) · Developmental Biology · doi:10.1016/j.ydbio.2018.05.013 · Cited by 202 · see citing works
Evolution of the ancestral mammalian karyotype and syntenic regions
Damas, J., Corbo, M., Kim, J., Turner-Maier, J., Farré, M., Larkin, D. M., Ryder, O. A., Steiner, C., Houck, M. L., Hall, S., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2209139119 · Cited by 91 · see citing works
Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis
Young, G. R., Stoye, J. P., & Kassiotis, G. (2013) · BioEssays · doi:10.1002/bies.201300049 · Cited by 78 · see citing works
“Also, loss of the eyes absent 1 (EYA1) gene in branchio-oto-renal syndrome and recurrent unbalanced translocations leading to intellectual disability have been shown to result from recombination between HERV-H copies [23, 24].”
BackgroundCampbell, I. M., Gambin, T., Dittwald, P., Beck, C. R., Shuvarikov, A., Hixson, P. M., Patel, A., Gambin, A., Shaw, C. A., Rosenfeld, J. A., et al. (2014) · BMC Biology · doi:10.1186/s12915-014-0074-4 · Cited by 69 · see citing works
Self-citationShuvarikov, A., Campbell, I. M., Dittwald, P., Neill, N. J., Bialer, M. G., Moore, C., Wheeler, P. G., Wallace, S. E., Hannibal, M., Murray, M. F., et al. (2013) · Human Mutation · doi:10.1002/humu.22384 · Cited by 47 · see citing works
Self-citationComprehensive analysis of syndromic hearing loss patients in Japan
Ideura, M., Nishio, S., Moteki, H., Takumi, Y., Miyagawa, M., Sato, T., Kobayashi, Y., Ohyama, K., Oda, K., Matsui, T., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-47141-4 · Cited by 45 · see citing works
Schmidt, T., Bierhals, T., Kortüm, F., Bartels, I., Liehr, T., Burfeind, P., Shoukier, M., Frank, V., Bergmann, C., & Kutsche, K. (2013) · Cytogenetic and Genome Research · doi:10.1159/000355436 · Cited by 41 · see citing works
Brophy, P. D., Alasti, F., Darbro, B. W., Clarke, J. C., Nishimura, C. J., Cobb, B., Smith, R. J., & Manak, J. R. (2013) · Human Genetics · doi:10.1007/s00439-013-1338-8 · Cited by 36 · see citing works
A recurrent translocation is mediated by homologous recombination between HERV-H elements
Hermetz, K. E., Surti, U., Cody, J. D., & Rudd, M. K. (2012) · Molecular Cytogenetics · doi:10.1186/1755-8166-5-6 · Cited by 27 · see citing works
Novel EYA1 variants causing Branchio-oto-renal syndrome
Klingbeil, K. D., Greenland, C. M., Arslan, S., Paneque, A. L., Gürkan, H., Ulusal, S. D., Maroofian, R., Carrera-Gonzalez, A., Montufar-Armendariz, S., Paredes, R., et al. (2017) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2017.04.037 · Cited by 22 · see citing works
Identification of a Novel CNV at 8q13 in a Family With Branchio‐Oto‐Renal Syndrome and Epilepsy
Men, M., Li, W., Chen, H., Wu, J., Feng, Y., Guo, H., & Li, J. (2019) · The Laryngoscope · doi:10.1002/lary.27941 · Cited by 22 · see citing works
Chen, X., Wang, J., Mitchell, E. B., Guo, J., Wang, L., Zhang, Y., Hodge, J. C., & Shen, Y. (2014) · BMC Medical Genetics · doi:10.1186/preaccept-1532986649107199 · Cited by 19 · see citing works
Chen, A., Song, J. H., Acke, F. R. E., Mei, L., Cai, X., Feng, Y., & He, C. (2021) · Clinical Genetics · doi:10.1111/cge.13949 · Cited by 16 · see citing works
Lin, C.-W., Ellegood, J., Tamada, K., Miura, I., Konda, M., Takeshita, K., Atarashi, K., Lerch, J. P., Wakana, S., McHugh, T. J., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01999-z · Cited by 13 · see citing works
Chang, H., Pan, Y., Landrette, S. F., Ding, S., Dong, Y., Liu, L., Tian, L., Chai, H., Li, P., Li, D., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906354116 · Cited by 12 · see citing works
HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entityPreprint
Giménez-Orenga, K., Martín‐Martínez, E., Nathanson, L., & Oltra, E. (2025) · eLife · doi:10.7554/elife.104441.3 · Cited by 12 · see citing works
Au, P. Y. B., Chernos, J. E., & Thomas, M. A. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37695 · Cited by 9 · see citing works
Baxi, A. B., Jourdeuil, K., Cox, T. C., Clouthier, D. E., & Tavares, A. L. P. (2023) · Developmental Dynamics · doi:10.1002/dvdy.597 · Cited by 7 · see citing works
Muthusamy, K., Hanna, C., Johnson, D. R., Cramer, C. H., Tebben, P. J., Libi, S. E., Poling, G. L., Lanpher, B. C., Morava, É., & Schimmenti, L. A. (2020) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61942 · Cited by 6 · see citing works
Endogenous Retroviruses and Coevolution
Mourikis, T. P., Aswad, A., & Katzourakis, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800049-6.00192-x · Cited by 6 · see citing works
Cacciatori, E., Aleo, S., Scuvera, G., Rigon, C., Marchisio, P., Cassina, M., & Milani, D. (2022) · The Italian Journal of Pediatrics/Italian journal of pediatrics · doi:10.1186/s13052-022-01369-5 · Cited by 5 · see citing works
Neal, S. J., Rajasekaran, A., Jusić, N., Taylor, L., Read, M., Alfandari, D., Pignoni, F., & Moody, S. A. (2023) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.23222 · Cited by 5 · see citing works
Kim, D. H., Yang, M., Jo, H. S., Park, J.-H., Jang, J., Shin, S., & Son, S.-H. (2022) · Children · doi:10.3390/children10010076 · Cited by 4 · see citing works
Cho, S. H., Jeong, S. H., Choi, W. H., & Lee, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158149 · Cited by 4 · see citing works
Zhang, H., Gao, J. H., Wang, H., Liu, M., Lu, S., Xu, H., Tang, W., & Zheng, G. (2024) · BMC Medical Genomics · doi:10.1186/s12920-024-01858-y · Cited by 4 · see citing works
Yi, H., Yun, Y., Choi, W. H., Hwang, H.-Y., Cha, J. H., Seok, H., Song, J., Lee, J. H., Oh, S. H., Lee, S.-Y., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102199 · Cited by 5 · see citing works
Auricular fistula: a review of its clinical manifestations, genetics, and treatments
Yuan, L., Yang, R., & Deng, H. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02343-2 · Cited by 3 · see citing works
Genetic research progress in branchio-oto syndrome/ branchio-oto-renal syndrome.
Chen, A., Ling, J., & Feng, Y. (2022) · PubMed Central · doi:10.11817/j.issn.1672-7347.2022.210251 · Cited by 3 · see citing works
Grelet, M., Mortreux, J., Alazard, E., Sigaudy, S., Philip, N., & Missirian, C. (2019) · Clinical Dysmorphology · doi:10.1097/mcd.0000000000000293 · Cited by 2 · see citing works
Branchio-oto-renal syndrome: a narrative review
Kumarasamy, G., Park, S. J., Park, P. G., Moon, I. S., & Shin, J. I. (2026) · Journal of the Korean Society of Pediatric Nephrology · doi:10.3339/ckd.25.039 · Cited by 1 · see citing works
Human Endogenous Retroviruses: Friends and Foes in Urology Clinics
Lee, S., Kim, S. H., & Ahnn, J. (2022) · International Neurourology Journal · doi:10.5213/inj.2244284.142 · Cited by 1 · see citing works
Hamilton, M., Sarkar, A., Dixit, A., & Marder, E. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37497
Wangsrimongkol, B. (2018) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Borges, A., Pinto‐Teixeira, F., Wibowo, I., Hammerschmidt, M., Kawakami, K., Miranda-Rodríguez, J. R., & López‐Schier, H. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.27.428404
Bonati, M. T., Feresin, A., Prontera, P., Michieletto, P., Gambacorta, V., Ricci, G., & Orzan, E. (2024) · Genes · doi:10.3390/genes15060677
Gao, X., Li, C., Yuan, F., Cao, X., Liu, C., Qi, W., Xie, F., & Xia, M. (2024) · Flavour and Fragrance Journal · doi:10.1002/ffj.3836
HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entityPreprint
Giménez-Orenga, K., Martín‐Martínez, E., Nathanson, L., & Oltra, E. (2025) · eLife · doi:10.7554/elife.104441.1
HERV activation segregates ME/CFS from fibromyalgia while defining a novel nosologic entityPreprint
Giménez-Orenga, K., Martín‐Martínez, E., Nathanson, L., & Oltra, E. (2025) · eLife · doi:10.7554/elife.104441.2
The Endogenisation of Retroviruses and Their Lasting Influence on Host Evolution
Harding, E. F., Mourikis, A., Aswad, A., & Katzourakis, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-15750-9.00164-6
- Authors
- Sanchez‐Valle, A., Wang, X., Potocki, L., Xia, Z., Kang, S. L., Carlin, M. E., Michel, D., Williams, P., Cabrera‐Meza, G., Brundage, E. K., Eifert, A. L., Stankiewicz, P., Cheung, S. W., & Lalani, S. R.
- Affiliations
- Baylor College of Medicine (US)
- Children's Medical Center (US)
- Corresponding author
- Lalani, Seema R.
- Venue
- American Journal of Medical Genetics Part A
- Publisher
- Wiley
- Published
- 2010-10-26
- Volume
- 152A
- Issue
- 11
- Pages
- 2854-2860
- ISSN
- 1552-4825 (ISSN-L)
- 1552-4833
- PMC
- PMC3605882
- OpenAlex
- W2047513249
- Cited by
- 43
- References
- 24
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part A (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Doris Duke Charitable Foundation
- Gillson Longenbaugh Foundation
- National Institute of General Medical Sciences (T32GM007526)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Genetics › Congenital Ear and Nasal Anomalies
- Health Sciences › Medicine › Surgery › Head and Neck Anomalies
- Keywords
- branchio-oto-renal syndrome, EYA1, human endogenous retroviruses, genome rearrangement, contiguous gene deletion, short stature, developmental delay, hearing loss, preauricular pits, renal anomalies
- MeSH terms
- Child, Child, Preschool, Chromosome Deletion, Female, Humans, Infant, Infant, Newborn, Male, Nuclear Proteins, Pregnancy, Gene Rearrangement, Genome, Human, Protein Tyrosine Phosphatases, Gene Deletion, Branchio-Oto-Renal Syndrome, Endogenous Retroviruses, Intracellular Signaling Peptides and Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Comparative Genomic Hybridization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
