A Beckwith-Wiedemann syndrome case with de novo 24\xa0Mb duplication of chromosome 11p15.5p14.3

Huling Jiang,Xiaodan Liu,Suping Li,Chiyan Zhou,Pinghua Huang,Ling Ai,Zepeng Ping,Yi Jin,Yuxia Jin,Jianguo Wang,Jie Chen

doi:10.1186/s13039-021-00532-7

Abstract

BackgroundMolecular genetic testing for the 11p15-associated imprinting disorder Beckwith-Wiedemann syndrome (BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. An integrated molecular approach to analyze the epigenetic-genetic alterations is required for accurate diagnosis of BWS.Case presentation: We reported a Chinese case with BWS detected by SNP array analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The genetic analysis showed a de novo duplication of 24 Mb at 11p15.5p14.3 is much longer than ever reported. MS-MLPA showed copy number changes with a peak height ratio value of 1.5 (three copies) at 11p15. The duplication of paternal origin with increase of methylation index of 0.68 at H19 and decreased methylation index of 0.37 at KCNQ1OT1.ConclusionCombined chromosome microarray analysis and methylation profiling provided reliable diagnosis for this paternally derived duplication of BWS. The phenotype associated with 11p15 duplications depends on the size, genetic content, parental inheritance and imprinting status. Identification of these rare duplications is crucial for genetic counselling.

Highlights

Beckwith-Wiedemann syndrome (BWS) (OMIM#130,650) is an imprinting disorder characterized by variable presence of macroglossia and over-growth, abdominal wall defects, hypoglycemia and embryonal tumor predisposition [1, 2]
MS‐MLPA Analysis methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis was used to validate the results observed with CMA
MSMLPA indicated methylation index of 0.68 at IC1 and methylation index of 0.37 at IC2 (Fig. 1c). We indentified this patient with duplication of the BWS critical region

Summary

Introduction

Beckwith-Wiedemann syndrome (BWS) (OMIM#130,650) is an imprinting disorder characterized by variable presence of macroglossia and over-growth, abdominal wall defects, hypoglycemia and embryonal tumor predisposition [1, 2]. Genetic analyses revealed that the patient harbored pUPD and copy number variation. This is a rare reported case of a patient with 24 Mb duplication, which is much longer than ever reported. Molecular genetic testing for the 11p15-associated imprinting disorder Beckwith-Wiedemann syndrome (BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. Case presentation: We reported a Chinese case with BWS detected by SNP array analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The genetic analysis showed a de novo duplication of 24 Mb at 11p15.5p14.3 is much longer than ever reported. MS-MLPA showed copy number changes with a peak height ratio value of 1.5 (three copies) at 11p15. The duplication of paternal origin with increase of methylation index of 0.68 at H19 and decreased methylation index of 0.37 at KCNQ1OT1

Methods

Results

Discussion

Conclusion