Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disordersCitation formats

  • External authors:
  • Rebecca L. Poole
  • Louise E. Docherty
  • Abeer Al Sayegh
  • Almuth Caliebe
  • Claire Turner
  • Emma Baple
  • Emma Wakeling
  • Lucy Harrison
  • Anna Lehmann
  • I. Karen Temple
  • Deborah J G Mackay

Standard

Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders. / Clayton, Peter; Poole, Rebecca L.; Docherty, Louise E.; Al Sayegh, Abeer; Caliebe, Almuth; Turner, Claire; Baple, Emma; Wakeling, Emma; Harrison, Lucy; Lehmann, Anna; Temple, I. Karen; Mackay, Deborah J G.

In: American Journal of Medical Genetics, Part A, Vol. 161, No. 9, 09.2013, p. 2174-2182.

Research output: Contribution to journalArticle

Harvard

Clayton, P, Poole, RL, Docherty, LE, Al Sayegh, A, Caliebe, A, Turner, C, Baple, E, Wakeling, E, Harrison, L, Lehmann, A, Temple, IK & Mackay, DJG 2013, 'Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders', American Journal of Medical Genetics, Part A, vol. 161, no. 9, pp. 2174-2182. https://doi.org/10.1002/ajmg.a.36049

APA

Clayton, P., Poole, R. L., Docherty, L. E., Al Sayegh, A., Caliebe, A., Turner, C., ... Mackay, D. J. G. (2013). Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders. American Journal of Medical Genetics, Part A, 161(9), 2174-2182. https://doi.org/10.1002/ajmg.a.36049

Vancouver

Clayton P, Poole RL, Docherty LE, Al Sayegh A, Caliebe A, Turner C et al. Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders. American Journal of Medical Genetics, Part A. 2013 Sep;161(9):2174-2182. https://doi.org/10.1002/ajmg.a.36049

Author

Clayton, Peter ; Poole, Rebecca L. ; Docherty, Louise E. ; Al Sayegh, Abeer ; Caliebe, Almuth ; Turner, Claire ; Baple, Emma ; Wakeling, Emma ; Harrison, Lucy ; Lehmann, Anna ; Temple, I. Karen ; Mackay, Deborah J G. / Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders. In: American Journal of Medical Genetics, Part A. 2013 ; Vol. 161, No. 9. pp. 2174-2182.

Bibtex

@article{d97f5c3dac1948b9b96d8a3da9ebe0dc,
title = "Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders",
abstract = "Imprinting disorders are associated with mutations and epimutations affecting imprinted genes, that is those whose expression is restricted by parent of origin. Their diagnosis is challenging for two reasons: firstly, their clinical features, particularly prenatal and postnatal growth disturbance, are heterogeneous and partially overlapping; secondly, their underlying molecular defects include mutation, epimutation, copy number variation, and chromosomal errors, and can be further complicated by somatic mosaicism and multi-locus methylation defects. It is currently unclear to what extent the observed phenotypic heterogeneity reflects the underlying molecular pathophysiology; in particular, the molecular and clinical diversity of multilocus methylation defects remains uncertain. To address these issues we performed comprehensive methylation analysis of imprinted genes in a research cohort of 285 patients with clinical features of imprinting disorders, with or without a positive molecular diagnosis. 20 of 91 patients (22{\%}) with diagnosed epimutations had methylation defects of additional imprinted loci, and the frequency of developmental delay and congenital anomalies was higher among these patients than those with isolated epimutations, indicating that hypomethylation of multiple imprinted loci is associated with increased diversity of clinical presentation. Among 194 patients with clinical features of an imprinting disorder but no molecular diagnosis, we found 15 (8{\%}) with methylation anomalies, including missed and unexpected molecular diagnoses. These observations broaden the phenotypic and epigenetic definitions of imprinting disorders, and show the importance of comprehensive molecular testing for patient diagnosis and management. {\circledC} 2013 Wiley Periodicals, Inc.",
keywords = "Angelman syndrome, Beckwith-Wiedemann syndrome, DNA methylation, Imprinting disorder, Prader willi syndrome, Pseudohypoparathyroidism type 1B, Silver-Russell syndrome, Transient neonatal diabetes, UPD14 mat, Wang syndrome",
author = "Peter Clayton and Poole, {Rebecca L.} and Docherty, {Louise E.} and {Al Sayegh}, Abeer and Almuth Caliebe and Claire Turner and Emma Baple and Emma Wakeling and Lucy Harrison and Anna Lehmann and Temple, {I. Karen} and Mackay, {Deborah J G}",
year = "2013",
month = "9",
doi = "10.1002/ajmg.a.36049",
language = "English",
volume = "161",
pages = "2174--2182",
journal = "American Journal of Medical Genetics. Part A",
issn = "1552-4825",
publisher = "John Wiley & Sons Ltd",
number = "9",

}

RIS

TY - JOUR

T1 - Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders

AU - Clayton, Peter

AU - Poole, Rebecca L.

AU - Docherty, Louise E.

AU - Al Sayegh, Abeer

AU - Caliebe, Almuth

AU - Turner, Claire

AU - Baple, Emma

AU - Wakeling, Emma

AU - Harrison, Lucy

AU - Lehmann, Anna

AU - Temple, I. Karen

AU - Mackay, Deborah J G

PY - 2013/9

Y1 - 2013/9

N2 - Imprinting disorders are associated with mutations and epimutations affecting imprinted genes, that is those whose expression is restricted by parent of origin. Their diagnosis is challenging for two reasons: firstly, their clinical features, particularly prenatal and postnatal growth disturbance, are heterogeneous and partially overlapping; secondly, their underlying molecular defects include mutation, epimutation, copy number variation, and chromosomal errors, and can be further complicated by somatic mosaicism and multi-locus methylation defects. It is currently unclear to what extent the observed phenotypic heterogeneity reflects the underlying molecular pathophysiology; in particular, the molecular and clinical diversity of multilocus methylation defects remains uncertain. To address these issues we performed comprehensive methylation analysis of imprinted genes in a research cohort of 285 patients with clinical features of imprinting disorders, with or without a positive molecular diagnosis. 20 of 91 patients (22%) with diagnosed epimutations had methylation defects of additional imprinted loci, and the frequency of developmental delay and congenital anomalies was higher among these patients than those with isolated epimutations, indicating that hypomethylation of multiple imprinted loci is associated with increased diversity of clinical presentation. Among 194 patients with clinical features of an imprinting disorder but no molecular diagnosis, we found 15 (8%) with methylation anomalies, including missed and unexpected molecular diagnoses. These observations broaden the phenotypic and epigenetic definitions of imprinting disorders, and show the importance of comprehensive molecular testing for patient diagnosis and management. © 2013 Wiley Periodicals, Inc.

AB - Imprinting disorders are associated with mutations and epimutations affecting imprinted genes, that is those whose expression is restricted by parent of origin. Their diagnosis is challenging for two reasons: firstly, their clinical features, particularly prenatal and postnatal growth disturbance, are heterogeneous and partially overlapping; secondly, their underlying molecular defects include mutation, epimutation, copy number variation, and chromosomal errors, and can be further complicated by somatic mosaicism and multi-locus methylation defects. It is currently unclear to what extent the observed phenotypic heterogeneity reflects the underlying molecular pathophysiology; in particular, the molecular and clinical diversity of multilocus methylation defects remains uncertain. To address these issues we performed comprehensive methylation analysis of imprinted genes in a research cohort of 285 patients with clinical features of imprinting disorders, with or without a positive molecular diagnosis. 20 of 91 patients (22%) with diagnosed epimutations had methylation defects of additional imprinted loci, and the frequency of developmental delay and congenital anomalies was higher among these patients than those with isolated epimutations, indicating that hypomethylation of multiple imprinted loci is associated with increased diversity of clinical presentation. Among 194 patients with clinical features of an imprinting disorder but no molecular diagnosis, we found 15 (8%) with methylation anomalies, including missed and unexpected molecular diagnoses. These observations broaden the phenotypic and epigenetic definitions of imprinting disorders, and show the importance of comprehensive molecular testing for patient diagnosis and management. © 2013 Wiley Periodicals, Inc.

KW - Angelman syndrome

KW - Beckwith-Wiedemann syndrome

KW - DNA methylation

KW - Imprinting disorder

KW - Prader willi syndrome

KW - Pseudohypoparathyroidism type 1B

KW - Silver-Russell syndrome

KW - Transient neonatal diabetes

KW - UPD14 mat, Wang syndrome

U2 - 10.1002/ajmg.a.36049

DO - 10.1002/ajmg.a.36049

M3 - Article

VL - 161

SP - 2174

EP - 2182

JO - American Journal of Medical Genetics. Part A

T2 - American Journal of Medical Genetics. Part A

JF - American Journal of Medical Genetics. Part A

SN - 1552-4825

IS - 9

ER -