Further understanding of paternal uniparental disomy in Beckwith-Wiedemann syndrome

ABSTRACT

Introduction

Paternal uniparental disomy of chromosome 11 (upd(11)pat) accounts for up to 20% of molecularly confirmed Beckwith-Wiedemann spectrum (BWSp) cases. It belongs to the BWSp subgroup with the second highest tumor risk, and therefore needs particular awareness in research, diagnostics and clinical management.

Areas covered

We overview the contribution of paternal (mosaic) uniparental disomy of chromosome 11 (UPD, upd(11)pat) and mosaic paternal uniparental diploidy in patients with Beckwith-Wiedemann features. The review comprises the current knowledge on their formation and their molecular and clinical consequences. Accordingly, the consequences for diagnostic testing and clinical monitoring are compiled.

Expert opinion

The necessity to diagnostically identify and thus discriminate genome-wide paternal uniparental disomy, and upd(11)pat becomes obvious, due to the differences in the clinical course, disease prognosis, and treatment. In particular, monitoring of tumor development by liquid biopsy might be a promising option in the future. From the research point of view, it should be addressed why 11p is prone to mitotic recombination and thus also provide to the role of upd(11) as second hit in tumorigenesis.

KEYWORDS:

• UPD
• BWSp
• paternal uniparental diploidy
• genomic imprinting

Article highlights

• Upd(11)pat is the molecular cause for 20% of BWS patients and is associated with a highly increased tumour risk.

• UPD originate as the product of a mitotic recombination or correction of a trisomic or monosomic cell in zygotes and have phenotypic consequences when they occur in chromosomal regions harboring imprinted genes and/or contain recessive gene mutations.

• Upd(11)pat is commonly the product of mitotic recombination errors, and therefore occurs as mosaic. Therefore, it is a challenge for diagnostic detection and might (clinically) affect only parts of the body or organ.

• Upd(11)pat has to be distinguished from a paternal uniparental diploidy, which has additional clinical consequences.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.