Coexistence of paternally-inherited ABCC8 mutation and mosaic paternal uniparental disomy 11p hyperinsulinism

International Journal of Pediatric Endocrinology
Joanna Yuet-Ling TungKelvin Yuen Kwong Chan

Abstract

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome with variable clinical phenotype and complex molecular aetiology. It is mainly caused by dysregulation of the chromosome 11p15 imprinted region, which results in overgrowth in multiple tissues, often in a mosaic manner. A large-for-gestational-age infant without any other somatic features of BWS presented with medically refractory hyperinsulinism (HI) requiring 80% pancreatectomy. Next generation sequencing with congenital HI sequencing panel identified a pathogenic ABCC8:c.1792C > T (p.Arg598Ter) variant of paternal origin, suggestive of focal HI. However, pancreatic histology revealed atypical findings of coalescing nests and trabeculae of adenomatosis scattered with islets with isolated enlarged, hyperchromatic nuclei scattered throughout the pancreas. Methylation analysis, SNP-based chromosomal microarray and short tandem repeat markers analysis revealed mosaic segmental paternal uniparental disomy (UPD) 11p15.5-p15.1 in the pancreatic tissue, but not the peripheral blood, suggestive of BWS/BW-spectrum HI. This case highlights the importance of integrating the clinical presentation and subsequent clinical course, together with radiological, genetic and histological...Continue Reading

References

Sep 18, 2008·The Journal of Clinical Endocrinology and Metabolism·L DamajF Jaubert
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Citations

Oct 27, 2020·Frontiers in Genetics·Chiara PapulinoLucia Altucci

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Methods Mentioned

BETA
pancreatectomy
PCR
genotyping

Software Mentioned

UPDtool

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Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is an imprinting disorder characterized by overgrowth, congenital malformations and predisposition to tumors. Discover the latest research on Beckwith-Wiedemann Syndrome here.