Asymmetry and skin pigmentary anomalies in chromosome mosaicism.

Woods, C. G.; Bankier, Agnes; Curry, John D.; Sheffield, Leslie J.; Slaney, Sarah F.; Smith, K.; Voullaire, Lucille; Wellesley, Diana

doi:10.1136/jmg.31.9.694

Cited by 70 publications

(80 citation statements)

References 35 publications

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“…More lenient detection thresholds may be preferred to increase detection sensitivity if clinical suspicion of mosaic duplication exists. Increasing the clonality of mosaicism by the biopsy of affected tissue, as is performed when pigmentary mosaicism provides evidence of underlying mosaicism (Woods et al 1994), should also theoretically improve detection. Given the size and clonality of the two missed events and the simulation results from whole-genome sequencing, both events would likely have been detected had they been analyzed using higher depth WES or WGS, which are likely to become more common in the future.…”

Section: Discussionmentioning

confidence: 99%

Detection of structural mosaicism from targeted and whole-genome sequencing data

et al. 2017

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Structural mosaic abnormalities are large post-zygotic mutations present in a subset of cells and have been implicated in developmental disorders and cancer. Such mutations have been conventionally assessed in clinical diagnostics using cytogenetic or microarray testing. Modern disease studies rely heavily on exome sequencing, yet an adequate method for the detection of structural mosaicism using targeted sequencing data is lacking. Here, we present a method, called MrMosaic, to detect structural mosaic abnormalities using deviations in allele fraction and read coverage from next-generation sequencing data. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) simulations were used to calculate detection performance across a range of mosaic event sizes, types, clonalities, and sequencing depths. The tool was applied to 4911 patients with undiagnosed developmental disorders, and 11 events among nine patients were detected. For eight of these 11 events, mosaicism was observed in saliva but not blood, suggesting that assaying blood alone would miss a large fraction, possibly >50%, of mosaic diagnostic chromosomal rearrangements.

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Section: Discussionmentioning

confidence: 99%

Detection of structural mosaicism from targeted and whole-genome sequencing data

et al. 2017

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“…Taking all of this patient's findings together with the preauricular tags/ pits, presentation was highly suggestive of a clinical diagnosis (2001) there was facial asymmetry/hypoplasia of one hemiface. Notwithstanding, we cannot rule out the possibility that this finding is associated with the chromosomal mosaicism exhibited by the patient, in which areas of hyperplasia and hypoplasia may occur (Woods et al, 1994). The frequency of heart defects observed in our sample (67%) was statistically similar to that of other series described in the literature, ranging from 50% to 63% (Berends et 2001) have rightly pointed out, these frequencies may have been affected by bias, since mildly affected patients may escape detection.…”

Section: Discussionmentioning

confidence: 99%

Características clínicas de uma amostra de pacientes com a síndrome do olho do gato

Rosa¹,

Mombach²,

Zen³

et al. 2010

Rev. Assoc. Med. Bras.

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“…The earlier the event occurs, the greater the individual's impairment is. Typically, phenotypic mosaic alterations never occur in all tissues, and thus, many of them are asymmetrical, and several present associated malformations, 21,22 as is observed in OAVS.…”

Section: Discussionmentioning

confidence: 99%

Clinical and cytogenetic features of a Brazilian sample of patients with phenotype of oculo-auriculo-vertebral spectrum: a cross-sectional study

et al. 2014

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CONTEXT AND OBJECTIVE: Oculo-auriculo-vertebral spectrum (OAVS) is considered to be a defect of embryogenesis involving structures originating from the first branchial arches. Our objective was to describe the clinical and cytogenetic findings from a sample of patients with the phenotype of OAVS. DESIGN AND SETTING: Cross-sectional study in a referral hospital in southern Brazil. METHODS:The sample consisted of 23 patients who presented clinical findings in at least two of these four areas: orocraniofacial, ocular, auricular and vertebral. The patients underwent a clinical protocol and cytogenetic evaluation through high-resolution karyotyping, fluorescence in situ hybridization for 5p and 22q11 microdeletions and investigation of chromosomal instability for Fanconi anemia. RESULTS: Cytogenetic abnormalities were observed in three cases (13%) and consisted of: 47,XX,+mar; mos 47,XX,+mar/46,XX; and 46,XX,t(6;10)(q13; q24). We observed cases of OAVS with histories of gestational exposition to fluoxetine, retinoic acid and crack. One of our patients was a discordant monozygotic twin who had shown asymmetrical growth restriction during pregnancy. Our patients with OAVS were characterized by a broad clinical spectrum and some presented atypical findings such as lower-limb reduction defect and a tumor in the right arm, suggestive of hemangioma/lymphangioma. CONCLUSIONS: We found a wide range of clinical characteristics among the patients with OAVS. Different chromosomal abnormalities and gestational expositions were also observed. Thus, our findings highlight the heterogeneity of the etiology of OAVS and the importance of these factors in the clinical and cytogenetic evaluation of these patients.RESUMO CONTEXTO E OBJETIVO: O espectro oculoauriculovertebral (EOAV) é considerado um defeito de embriogênese envolvendo estruturas originadas a partir dos primeiros arcos branquiais. Nosso objetivo foi descrever os achados clínicos e citogenéticos de uma amostra de pacientes com fenótipo de EOAV. TIPO DE ESTUDO E LOCAL: Estudo transversal em um hospital de referência no sul do Brasil. MÉTODOS: A amostra foi composta de 23 pacientes que apresentaram achados clínicos em pelo menos duas das quatro áreas: orocraniofacial, oculares, auriculares e vertebrais. Os pacientes foram submetidos a um protocolo clínico e avaliação citogenética através do cariótipo de alta resolução, hibridização in situ fluorescente para as microdeleções 5p e 22q11 e pesquisa de instabilidade cromossômica para anemia de Fanconi. RESULTADOS: Alterações citogenéticas foram observadas em três casos (13%) e consistiam de: 47,XX,+mar; mos 47,XX,+mar/46,XX e 46,XX,t(6;10)(q13;q24). Observamos casos de EOAV com história de exposição gestacional à fluoxetina, ácido retinoico e crack. Um dos nossos pacientes foi um gêmeo monozigótico discordante que teve restrição de crescimento assimétrica durante a gravidez. Nossos pacientes com EOAV foram caracterizados por um amplo espectro clínico e alguns apresentaram achados clínicos atípicos como um defeito de reduç...

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Asymmetry and skin pigmentary anomalies in chromosome mosaicism.

Cited by 70 publications

References 35 publications

Detection of structural mosaicism from targeted and whole-genome sequencing data

Detection of structural mosaicism from targeted and whole-genome sequencing data

Características clínicas de uma amostra de pacientes com a síndrome do olho do gato

Clinical and cytogenetic features of a Brazilian sample of patients with phenotype of oculo-auriculo-vertebral spectrum: a cross-sectional study

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