Genomic rearrangements of EYA1 account for a large fraction of families with BOR syndrome

Vervoort, Virginie; Smith, Richard J.H.; O’Brien, Judith A.; Schroer, Richard J.; Abbott, Albert G.; Stevenson, Roger E.; Schwartz, Charles E.

doi:10.1038/sj.ejhg.5200877

Cited by 50 publications

(47 citation statements)

References 29 publications

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“…31 Several previous studies reported a much lower detection rate of EYA1 mutations of 25 -40% in BOR patients with the highest success rate in familial cases. 3,15,34,35 The absence of EYA1 abnormalities detectable by MLPA, which was applied for the first time in the present study, does not support the previous suggestion of a 20% frequency of complex rearrangements of EYA1 as causative in BOR. 15 More reliable figures for the proportion of patients having deletions or duplications, detectable by MLPA, and the proportion having BOR due to SIX1 mutations can only be reached by studying more patients.…”

Section: Discussioncontrasting

confidence: 99%

“…14 At least 116 different EYA1 mutations and rearrangements have been reported (isoform B). 3,15,16 By contrast, only few mutations have been reported in the SIX genes. Thus, so far, five unrelated families have been published with three different mutations in SIX1, 10,17 and five BOR individuals have been identified with four different SIX5 missense mutations.…”

Section: Introductionmentioning

confidence: 99%

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Branchio–oto–renal syndrome: detection of EYA1 and SIX1 mutations in five out of six Danish families by combining linkage, MLPA and sequencing analyses

et al. 2007

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The branchio -oto -renal (BOR) syndrome is an autosomal-dominant disorder characterized by hearing loss, branchial and renal anomalies. BOR is genetically heterogeneous and caused by mutations in EYA1 (8q13.3), SIX1 (14q23.1), SIX5 (19q13.3) and in an unidentified gene on 1q31. We examined six Danish families with BOR syndrome by assessing linkage to BOR loci, by performing EYA1 multiplex ligationdependent probe amplification (MLPA) analysis for deletions and duplications and by sequencing of EYA1, SIX1 and SIX5. We identified four EYA1 mutations (c.920delG, IVS10À1G4A, IVS12 þ 4A4G and p.Y591X) and one SIX1 mutation (p.W122R), providing a molecular diagnosis in five out of the six families (83%). The present, yet preliminary, observation that renal and temporal bone malformations are less frequent in SIX1-related disease suggests a slightly different clinical profile compared to EYA1-related disease. Unidentified mutations impairing mRNA expression or further genetic heterogeneity may explain the lack of mutation finding in one family despite LOD score indications of EYA1 involvement.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Branchio–oto–renal syndrome: detection of EYA1 and SIX1 mutations in five out of six Danish families by combining linkage, MLPA and sequencing analyses

et al. 2007

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“…Three human cases, however, have been identified in which heterozygous mutation of EYA1 correlates with anterior segment defects (Azuma et al, 2000). Additional insight into the mechanism for this human defect is needed, however, since many other mutations in EYA1 have been reported that have no effect on eye development (Vervoot et al, 2002). Hopefully these mutations will ultimately provide insight into the function of Eya genes in the vertebrate eye.…”

Section: Synergism With Eyamentioning

confidence: 99%

Conservation and non-conservation of genetic pathways in eye specification

Donner¹,

Maas

2004

Int. J. Dev. Biol.

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In this review we highlight two genetic pathways important for eye morphogenesis that are partially conserved between flies and vertebrates. Initially we focus on the ey paradigm and establish which aspects of this genetic hierarchy are conserved in vertebrates. We discuss experiments that evaluate the non-linear relationship amongst the genes of the hierarchy with a concentration on vertebrate functional genetics. We specifically consider the Six genes and their relationship to sine oculis, as tremendous amounts of new data have emerged on this topic. Finally, we highlight similarities between Shh/Hh directed morphogenesis mediated by basic Helix-LoopHelix factors in vertebrate retinal cell specification and in specification of fly photoreceptors.

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“…The authors have suggested that these changes could be related with the acquisition of hearing acuity necessary for understanding spoken language, and they emphasize the importance of further research into hearing differences between humans and chimpanzees (3). At least one of the human genes mentioned as having undergone adaptive evolutionary change (EYA1) is related to the development of the outer and middle ear (4,5). These results are compatible with the known differences in the anatomical structures of the outer and middle ear in chimpanzees and ourselves (6,7).…”

mentioning

confidence: 99%

Auditory capacities in Middle Pleistocene humans from the Sierra de Atapuerca in Spain

Martı́nez

Rosa

Arsuaga

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

143

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Human hearing differs from that of chimpanzees and most other anthropoids in maintaining a relatively high sensitivity from 2 kHz up to 4 kHz, a region that contains relevant acoustic information in spoken language. Knowledge of the auditory capacities in human fossil ancestors could greatly enhance the understanding of when this human pattern emerged during the course of our evolutionary history. Here we use a comprehensive physical model to analyze the influence of skeletal structures on the acoustic filtering of the outer and middle ears in five fossil human specimens from the Middle Pleistocene site of the Sima de los Huesos in the Sierra de Atapuerca of Spain. Our results show that the skeletal anatomy in these hominids is compatible with a human-like pattern of sound power transmission through the outer and middle ear at frequencies up to 5 kHz, suggesting that they already had auditory capacities similar to those of living humans in this frequency range.K nowledge about the sensory capabilities of past life forms could greatly enhance our understanding of the adaptations and lifeways in extinct organisms. Audition is the most readily accessible in fossils because it is based primarily in physical properties that can be approached through their skeletal structures (1). Recently, the possibility to analyze auditory capacities in fossil species has been highlighted as one of the major challenges in modern vertebrate paleontology, particularly since the advent of computed tomography (CT)-based analyses (2).The recent publication of a detailed comparison of the human and chimpanzee genomes has highlighted several genes involved with hearing that appear to have undergone adaptive evolutionary changes in the human lineage (3). The authors have suggested that these changes could be related with the acquisition of hearing acuity necessary for understanding spoken language, and they emphasize the importance of further research into hearing differences between humans and chimpanzees (3). At least one of the human genes mentioned as having undergone adaptive evolutionary change (EYA1) is related to the development of the outer and middle ear (4, 5). These results are compatible with the known differences in the anatomical structures of the outer and middle ear in chimpanzees and ourselves (6, 7).As might be expected from these genetic and anatomical data, the empirical studies of chimpanzee hearing capabilities also show clear differences with human hearing. Chimpanzee audiograms (8, 9) show a W-shaped pattern characterized by two peaks of high sensitivity at Ϸ1 kHz and 8 kHz, respectively, and a relative loss of sensitivity in the midrange frequencies (between 2 and 4 kHz). Of course, this relative loss does not mean that chimpanzees cannot hear in the midrange frequencies, but rather that they are adapted to hear best at Ϸ1 kHz and 8 kHz. It is interesting to note that the species-specific pant-hoots regularly emitted by wild chimpanzees to communicate with conspecifics over long distances concentrate the acoustic ...

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Genomic rearrangements of EYA1 account for a large fraction of families with BOR syndrome

Cited by 50 publications

References 29 publications

Branchio–oto–renal syndrome: detection of EYA1 and SIX1 mutations in five out of six Danish families by combining linkage, MLPA and sequencing analyses

Branchio–oto–renal syndrome: detection of EYA1 and SIX1 mutations in five out of six Danish families by combining linkage, MLPA and sequencing analyses

Conservation and non-conservation of genetic pathways in eye specification

Auditory capacities in Middle Pleistocene humans from the Sierra de Atapuerca in Spain

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