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

TitleCoexistence of paternally-inherited ABCC8 mutation and mosaic paternal uniparental disomy 11p hyperinsulinism
Authors
KeywordsCongenital hyperinsulinism
Hyperinsulinism
Beckwith-Wiedemann syndrome
UPD11
Issue Date2020
PublisherBMC. The Journal's web site is located at http://www.ijpeonline.com/
Citation
International Journal of Pediatric Endocrinology, 2020, v. 2020, p. article no. 13 How to Cite?
AbstractBackground: 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. Case presentation: 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. Conclusions: This case highlights the importance of integrating the clinical presentation and subsequent clinical course, together with radiological, genetic and histological findings in the definitive diagnosis of this rare yet clinically important entity. In addition, this is the first report that demonstrated the level of paternal inherited c.1792 T pathogenic variant in the pancreatic tissue being directly correlated to the mosaic level of pUPD.
Persistent Identifierhttp://hdl.handle.net/10722/284107
ISSN

 

DC FieldValueLanguage
dc.contributor.authorTung, JYL-
dc.contributor.authorLai, SHY-
dc.contributor.authorAu, SLK-
dc.contributor.authorYeung, KS-
dc.contributor.authorKan, ASY-
dc.contributor.authorLoong, F-
dc.contributor.authorDeLeon, DD-
dc.contributor.authorKalish, JM-
dc.contributor.authorGanguly, A-
dc.contributor.authorChung, BHY-
dc.contributor.authorChan, KYK-
dc.date.accessioned2020-07-20T05:56:09Z-
dc.date.available2020-07-20T05:56:09Z-
dc.date.issued2020-
dc.identifier.citationInternational Journal of Pediatric Endocrinology, 2020, v. 2020, p. article no. 13-
dc.identifier.issn1687-9856-
dc.identifier.urihttp://hdl.handle.net/10722/284107-
dc.description.abstractBackground: 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. Case presentation: 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. Conclusions: This case highlights the importance of integrating the clinical presentation and subsequent clinical course, together with radiological, genetic and histological findings in the definitive diagnosis of this rare yet clinically important entity. In addition, this is the first report that demonstrated the level of paternal inherited c.1792 T pathogenic variant in the pancreatic tissue being directly correlated to the mosaic level of pUPD.-
dc.languageeng-
dc.publisherBMC. The Journal's web site is located at http://www.ijpeonline.com/-
dc.relation.ispartofInternational Journal of Pediatric Endocrinology-
dc.rightsInternational Journal of Pediatric Endocrinology. Copyright © BMC.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCongenital hyperinsulinism-
dc.subjectHyperinsulinism-
dc.subjectBeckwith-Wiedemann syndrome-
dc.subjectUPD11-
dc.titleCoexistence of paternally-inherited ABCC8 mutation and mosaic paternal uniparental disomy 11p hyperinsulinism-
dc.typeArticle-
dc.identifier.emailTung, JYL: tungylj@hku.hk-
dc.identifier.emailLai, SHY: sophiehy@HKUCC-COM.hku.hk-
dc.identifier.emailAu, SLK: alkuen@hku.hk-
dc.identifier.emailYeung, KS: ksyyeung@hku.hk-
dc.identifier.emailKan, ASY: kansya@hkucc.hku.hk-
dc.identifier.emailChung, BHY: bhychung@hku.hk-
dc.identifier.emailChan, KYK: ykchanc@hku.hk-
dc.identifier.authorityChung, BHY=rp00473-
dc.identifier.authorityChan, KYK=rp00453-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13633-020-00083-5-
dc.identifier.hkuros311278-
dc.identifier.volume2020-
dc.identifier.spagearticle no. 13-
dc.identifier.epagearticle no. 13-
dc.publisher.placeUnited Kingdom-

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