Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood

Alders, Mariëlle; Maas, Saskia M.; Kadouch, Daniel J.; Lip, Karin van der; Bliek, Jet; Horst, Chantal M.A.M. van der; Mannens, Marcel M.A.M.

doi:10.1016/j.ejmg.2014.03.011

Cited by 29 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This discrepancy is in accordance with a previous report on the mosaic distributions of molecular disturbances in BWS. 14 The example vividly illustrates that laboratories offering prenatal (and postnatal) tests have to be aware of and to report on the risk to miss 11p15 defects owing to somatic mosaicism and the value of prenatal testing has to be critically discussed with the families.…”

Section: Prenatal Testing Results and Pregnancy Outcomementioning

confidence: 99%

“…A negative prenatal test result As already discussed, the major molecular alterations both in BWS and SRS (ie, epimutations in SRS/BWS and upd(11)pat in BWS) can occur in the mosaic form 14,21 and might escape molecular detection because of the low level of cells harboring the disturbance. The authors are aware of two false-negative prenatal testing result with an epimutation detected after birth (Table 3b).…”

Section: A Positive Prenatal Test Resultsmentioning

confidence: 99%

“…13 Mosaicism can disturb genotype-phenotype correlations and may explain, in part, the broad phenotypic range associated with these disorders (Table 1). From the diagnostic point of view, it can significantly hamper the detection of the molecular alteration (eg, Alders et al 14 ). Therefore, it is in principle impossible to exclude the clinical diagnosis in case of a negative test result, because other untested tissues might carry the alteration.…”

Section: Molecular Alterations In Ids and Mosaicismmentioning

confidence: 99%

See 2 more Smart Citations

Prenatal molecular testing for Beckwith–Wiedemann and Silver–Russell syndromes: a challenge for molecular analysis and genetic counseling

et al. 2015

Self Cite

View full text Add to dashboard Cite

15Beckwith-Wiedemann and Silver-Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in 470% of patients, whereas in SRS they are observed in about 60% of the cases. In addition, 10% of the SRS patients carry a maternal uniparental disomy of chromosome 7 11p15.5. There is an increasing demand for prenatal testing of these disorders owing to family history, indicative prenatal ultrasound findings or aberrations involving chromosomes 7 and 11. The complex molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge concerning the inheritance and recurrence risks for the epigenetic abnormalities, which are hallmarks of these developmental disorders. In this paper, experts in the field of BWS and SRS, including members of the European network of congenital IDs (EUCID.net; www.imprinting-disorders.eu), put together their experience and work in the field of 11p15.5-associated IDs with a focus on prenatal testing. Altogether, prenatal tests of 160 fetuses (122 referred for BWS, 38 for SRS testing) from 5 centers were analyzed and reviewed. We summarize the current knowledge on BWS and SRS with respect to diagnostic testing, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders.

show abstract

Section: Prenatal Testing Results and Pregnancy Outcomementioning

confidence: 99%

Section: A Positive Prenatal Test Resultsmentioning

confidence: 99%

Section: Molecular Alterations In Ids and Mosaicismmentioning

confidence: 99%

See 1 more Smart Citation

Prenatal molecular testing for Beckwith–Wiedemann and Silver–Russell syndromes: a challenge for molecular analysis and genetic counseling

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…This is particularly recognized for epimutations in SRS and BWS. The level of mosaicism shows a broad range, and can differ remarkably between different tissues [15,16]. Therefore, if the tissue source of the diagnostic DNA sample has a level of mosaicism below the sensitivity of the diagnostic test, the result will be negative and the patient will escape diagnosis.…”

Section: Limitation 2: Heterogeneity Of the Aetiology In Idsmentioning

confidence: 99%

“…In particular in the 11p15-associated disorders (BWS and SRS), nearly all patients with epimutations and UPD show mosaicism (for review: [13]). As a consequence of mosaicism, the molecular alterations currently often escape diagnostic detection in case of a low level mosaicism [30], an unequal distribution in different tissues [15], or an insufficient sensitivity of assays [31,32]. New diagnostic approaches therefore may analyze different tissues from the same patient as well as apply multilocus and/or deep-sequencing tests.…”

Section: Translational Use Of New Techniques In Idsmentioning

confidence: 99%

Congenital imprinting disorders: Application of multilocus and high throughput methods to decipher new pathomechanisms and improve their management

Soellner

Monk

Rezwan

et al. 2015

Molecular and Cellular Probes

View full text Add to dashboard Cite

Imprinting disorders (IDs) are a group of congenital diseases affecting growth, development and metabolism. They are caused by changes in the allele-specific regulation ("epigenetic mutation") or in the genomic sequence ("genetic mutation") of imprinted genes. Currently molecular tests in ID patients are generally restricted to single loci classically associated with the disease, but this approach limits diagnostic yield, because of the molecular and clinical heterogeneity between IDs. From the technical point of view, these limitations are aggravated by the lack of standardization in testing methodology, in the DNA sequences tested, and in clinical inclusion criteria prompting testing.However, an increasing number of new studies show that these problems can be addressed by the use of new tests targeting multiple loci and/or a total exome and genome analysis.The rapid development of efficient and high-throughput molecular techniques and their applications in research and diagnostics in the last decade have led to an impressive increase of knowledge on IDs and their basic pathomechanisms. In combination with the improvement of data recording and documentation, the diagnostic strategies are increasingly based on standardized protocols, and thereby provide the backbone for directed counselling, more personalized management, and new therapeutic approaches.

show abstract

Characterization of the Beckwith‐Wiedemann spectrum: Diagnosis and management

Duffy

Cielo

Cohen

et al. 2019

American J of Med Genetics Pt C

View full text Add to dashboard Cite

Beckwith‐Wiedemann syndrome (BWS) is the most common epigenetic overgrowth and cancer predisposition disorder. Due to both varying molecular defects involving chromosome 11p15 and tissue mosaicism, patients can present with a variety of clinical features, leading to the newly defined Beckwith‐Wiedemann spectrum (BWSp). The BWSp can be further divided into three subsets of patients: those presenting with classic features, those presenting with isolated lateralized overgrowth (ILO) and those not fitting into the previous two categories, termed atypical BWSp. Previous reports of patients with BWS have focused on those with the more recognizable, classic features, and limited information is available on those who fit into the atypical and ILO categories. Here, we present the first cohort of patients recruited across the entire BWSp, describe clinical features and molecular diagnostic characteristics, and provide insight into practical diagnosis and management recommendations that we have gained from this cohort.

show abstract

Methylation analysis in tongue tissue of BWS patients identifies the (EPI)genetic cause in 3 patients with normal methylation levels in blood

Cited by 29 publications

References 18 publications

Prenatal molecular testing for Beckwith–Wiedemann and Silver–Russell syndromes: a challenge for molecular analysis and genetic counseling

Prenatal molecular testing for Beckwith–Wiedemann and Silver–Russell syndromes: a challenge for molecular analysis and genetic counseling

Congenital imprinting disorders: Application of multilocus and high throughput methods to decipher new pathomechanisms and improve their management

Characterization of the Beckwith‐Wiedemann spectrum: Diagnosis and management

Contact Info

Product

Resources

About