ORCID Profile
0000-0003-3088-4401
Current Organisation
University of Southampton
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Publisher: Springer Science and Business Media LLC
Date: 21-04-2015
Publisher: Wiley
Date: 23-11-2014
DOI: 10.1111/JPC.12778
Abstract: Silver-Russell syndrome (SRS) and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome are described in isolation. However, their co-occurrence has only been rarely reported. Here, we present a case report of an adolescent with SRS who was diagnosed with MRKH during the evaluation of primary amenorrhoea. Multiplex ligation-dependent probe lification analysis showed a normal methylation pattern and normal dosage at 11p15.5. A PubMed search for all peer-reviewed publications (original articles and reviews) using the key words Silver-Russell syndrome, Mayer-Rokitansky-Küster-Hauser syndrome, genetics, hypomethylation and reproductive anomalies identified three cases of SRS with MRKH, two of which were associated with significant hypomethylation of the H19 imprinting control region of the 11p15.5 locus. This report highlights the association between SRS and MRKH. The absence of hypomethylation and normal dosage at 11p15.5 suggests these two rare entities share alternative aetiopathogenic mechanisms.
Publisher: BMJ
Date: 05-02-2014
Publisher: Cold Spring Harbor Laboratory
Date: 03-06-2019
Abstract: Germline mutations in fundamental epigenetic regulatory molecules including DNA methyltransferase 3 alpha ( DNMT3A ) are commonly associated with growth disorders, whereas somatic mutations are often associated with malignancy. We profiled genome-wide DNA methylation patterns in DNMT3A c.2312G A p.(Arg771Gln) carriers in a large Amish sibship with Tatton-Brown–Rahman syndrome (TBRS), their mosaic father, and 15 TBRS patients with distinct pathogenic de novo DNMT3A variants. This defined widespread DNA hypomethylation at specific genomic sites enriched at locations annotated as genes involved in morphogenesis, development, differentiation, and malignancy predisposition pathways. TBRS patients also displayed highly accelerated DNA methylation aging. These findings were most marked in a carrier of the AML-associated driver mutation p.Arg882Cys. Our studies additionally defined phenotype-related accelerated and decelerated epigenetic aging in two histone methyltransferase disorders: NSD1 Sotos syndrome overgrowth disorder and KMT2D Kabuki syndrome growth impairment. Together, our findings provide fundamental new insights into aberrant epigenetic mechanisms, the role of epigenetic machinery maintenance, and determinants of biological aging in these growth disorders.
Publisher: BMJ
Date: 07-2004
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.CELL.2019.02.040
Abstract: The introduction of exome sequencing in the clinic has sparked tremendous optimism for the future of rare disease diagnosis, and there is exciting opportunity to further leverage these advances. To provide diagnostic clarity to all of these patients, however, there is a critical need for the field to develop and implement strategies to understand the mechanisms underlying all rare diseases and translate these to clinical care.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Deborah JG Mackay.