Histone acetylation dependent allelic expression imbalance of BAPX1 in patients with the oculo-auriculo-vertebral spectrum

Fischer, Sven; Lüdecke, Hermann‐Josef; Wieczorek, Dagmar; Böhringer, Stefan; Gillessen‐Kaesbach, Gabriele; Horsthemke, Bernhard

doi:10.1093/hmg/ddi474

Cited by 69 publications

(57 citation statements)

References 38 publications

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“…6 The heterogeneity of this condition has been further supported by the observation that epigenetic deregulation is associated with the occurrence of OAVS. 16 Although we observed three positive regions after we have analyzed all the members of F2, an LOD score of 3.0 was only observed with markers of chromosome 1. The LOD score of 3.01 observed with the marker D1S252 is the maximum possible LOD-score value that can be obtained in F2, assuming full penetrance.…”

Section: -15mentioning

confidence: 75%

Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity

Masotti

Oliveira

Poerner³

et al. 2007

Eur J Hum Genet

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Auriculo-condylar syndrome (ACS), an autosomal dominant disorder of first and second pharyngeal arches, is characterized by malformed ears ('question mark ears'), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia. Penetrance seems to be complete, but there is high inter-and intra-familial phenotypic variation, with no evidence of genetic heterogeneity. We herein describe a new multigeneration family with 11 affected individuals (F1), in whom we confirm intra-familial clinical variability. Facial asymmetry, a clinical feature not highlighted in other ACS reports, was highly prevalent among the patients reported here. The gene responsible for ACS is still unknown and its identification will certainly contribute to the understanding of human craniofacial development. No chromosomal rearrangements have been associated with ACS, thus mapping and positional cloning is the best approach to identify this disease gene. To map the ACS gene, we conducted linkage analysis in two large ACS families, F1 and F2 (F2; reported elsewhere). Through segregation analysis, we first excluded three known loci associated with disorders of first and second pharyngeal arches (Treacher Collins syndrome, oculo-auriculo-vertebral spectrum, and Townes-Brocks syndrome). Next, we performed a wide genome search and we observed evidence of linkage to 1p21.1-q23.3 in F2 (LOD max 3.01 at h ¼ 0). Interestingly, this locus was not linked to the phenotype segregating in F1. Therefore, our results led to the mapping of a first locus of ACS (ACS1) and also showed evidence for genetic heterogeneity, suggesting that there are at least two loci responsible for this phenotype.

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Section: -15mentioning

confidence: 75%

Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity

Masotti

Oliveira

Poerner³

et al. 2007

Eur J Hum Genet

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“…Therefore, studies of additional families are of importance to the identification of the loci involved. Fischer et al (2006) found abnormal BAPX1 expression in a significant number of OAVS patients and suggested that epigenetic disregulation of BAPX1 might play a role in the etiology of OAVS. In addition, a few patients showing clinical overlap with OAVS had mutations in sal-like 1 (SALL1) (Kohlhase et al 1999;Keegan et al 2001;Kosaki et al 2007) or Treacher Collins-Franceschetti syndrome 1 (TCOF1) (Su et al 2007), the genes responsible for most cases of Townes-Brocks syndrome [OMIM 107480] and Treacher Collins syndrome [OMIM 154500], respectively, which are also associated with first and second branchial arch anomalies.…”

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confidence: 97%

Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

Huang

Tan

et al. 2010

Tohoku J. Exp. Med.

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Oculo-auriculo-vertebral spectrum (OAVS) is a common developmental disorder involving first and second pharyngeal arches. Although some family cases and such patients showing chromosomal aberrations suggest that OAVS have a genetic basis, no consistent genetic defects have been recorded at present time. Thus, we conducted genetic studies of a three-generation family with five OAVS patients to identify a causative variant for OAVS. Cytogenetic studies revealed those family members had a normal karyotype and no causative mutations were founded in SALL1 and TCOF1 , which known to be responsible for two other syndromes that have clinical overlapping with OAVS. Genotyping with commercially available BeadChips was performed on 13 individuals in the same family, showing no significant difference between the affected and normal members in terms of copy number variations (CNVs) in either number or size and no definitive causative CNV. A total of 8,224 informative autosomal SNPs that are evenly distributed throughout the genome were selected for both parametric and non-parametric linkage analysis. Significant negative LOD scores were obtained for the reported OAVS locus, providing further evidence for genetic heterogeneity of this complex disorder. The highest LOD score of 1.60 was noted on chromosome 15q26.2-q26.3 showing a potential linkage to this locus. The variable phenotypes of the affected members and the failure to identify a causative variant indicate that a complex etiology may be present even in a consanguineous family, which makes it more challenging to ascertain the cause of OAVS in further analysis.

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“…Therefore it is possible that in our patient multiple gene mutations possibly contiguous may have caused the OAVS, via malregutation of NCC development or migration, or via abnormal integration of NCC with mesodermal structures present in branchial arches and may have caused precocious puberty via hypothalamic-pituitary axis functional malregulation. Other studies have suggested a role of the Goosecoid gene (in chromosome 14q32) in hemifacial microsomia development 42 and of BAPXI gene 43 . In OAVS development further studies could indicate the abnormal genetic ground present in our patient, but NCC pathology seems to play a major role in OAVS.…”

Section: Discussionmentioning

confidence: 96%

Precocious puberty in a patient with Oculo-Auriculo-Verebral spectrum (OAVS)

2014

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The authors report on the first case of OAVS (Oculo-AuriculoVertebral-Spectrum), with hemifacial microsomy, hydrocephalus, pubertas precox, thelarche at 4 years of age, vaginal bleeding at 5 years, and left ovary of adult type on echography (right ovary initially not visualized). FISH and CGH-ARRAYS methods were negative. By GnRH therapy the delay of onset puberty was obtained. The authors ascribe facial and ovary asymmetry to a derangement of blastogenesis, during which axial right-left structures begin the develop with consequent migration or interation with surrounding tissues of neural crest cells and alteration of diencephalic pituitary systems. RiassuntoGli autori riportano il primo caso della letteratura di OAVS (OculoAuriculo-Vertebral-Spectrum) con asimmetria facciale, idrocefalo e pubertà precoce, con telarca insorto a 4 anni, perdite ematiche vaginali a 5 anni ed ovaio sn di tipo adulto, mentre il destro non era inizialmente visualizzato e negativi erano FISH e ARRAYS -CGH. Attribuiscono l'asimmetria facciale ed ovarica nella bambina ad un disturbo nella blastogenesi, epoca in cui si determinano gli assi corporei destro-sinistro, con successiva anomalia nella migrazione ed interazione delle cellule delle creste neurali con i tessuti ed in particolare con l'ipofisi ed il diencefalo.Segnalano i risultati positivi ottenuti sul rallentamento della pubertà mediante preparati a base di Gn RH.Oculo-auriculo-vertebral spectrum (OAVS) is relatively common condition, involving the structures derived from the branchial arches, but also other organs 1 We report on the first case of OAVS with precocious puberty. Family history of the patient, a female, included an aunt of her grandmother with right eye proptosis and microphthalmia, her mother with hearing loss, a brother with right hemifacial microsomia and right eye slight than left. The mother showed precocious cessation of menstruations (at 35 years of age). The patient was born by caesarean section, birth weight was 3150 gr, head circumference 38 cm. The baby presented respiratory distress, bilateral pes talo-valgus, feeding difficulties in the first months of life delayed developmental milestones, and frequent otitis. At 1 years 7 months of life, physical examination showed a female (Fig.1) in the 75 th percentile for height and in the 90 th percentile for weight (Italian growth charts). Frontal bossing, right eye microphthalmia with eyelid ptosis and strabismus were present. Palpebral fissures showed slight antimongoloid slant; eye movements were normal bilaterally. The face was asymmetric, with hemifacial microsomia, the chin was receding; mild malar hypoplasia, and the right ear set at a lower level than the left one were present. Ears presented bilaterally simple, with hypoplastic lobules, and were low set (Fig.2). Nasal root was flat and nasal pyramid was downturned. Malocclusion due to mandibular asymmetry, macrostomia, overjet and difficulties in chewing and swallowing were present. Teeth were small with some enamel dysplasias. The voice was na...

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Histone acetylation dependent allelic expression imbalance of BAPX1 in patients with the oculo-auriculo-vertebral spectrum

Cited by 69 publications

References 38 publications

Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity

Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity

Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

Precocious puberty in a patient with Oculo-Auriculo-Verebral spectrum (OAVS)

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