The SINEs were there: identification of a pathogenic Alu insertion in a patient with DICER1-related tumour predisposition

variants, with no detectable germline variant, complicating the genetic diagnosis.A structural variant (SV) initially detected in a tumour sample prompted retrospective review of alignment data from all previously tested tumour, blood and normal tissue samples. This revealed a consistent SV across all samples. Short-read data suggested the SV was an Alu element insertion within the RNase IIIa domain of DICER1, but read length was insufficient for conclusive characterisation.Subsequent long-read nanopore sequencing confirmed a pathogenic AluY insertion, predicted to disrupt DICER1 function.This case highlights the importance of comprehensive genomic and functional analyses, especially in unresolved cases with strong clinical suspicion. It also demonstrates the value of long-read sequencing in identifying complex variants missed by conventional approaches.

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Publication Details

Journal
Journal of Medical Genetics
Published
2026-03-31
DOI
https://doi.org/10.1136/jmg-2025-111365
Primary Topic
Congenital Diaphragmatic Hernia Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

The SINEs were there: identification of a pathogenic Alu insertion in a patient with DICER1-related tumour predisposition

Hood Mugalaasi, Mikel Valganon-Petrizan, Helen Hanson, Oluwatosin Taiwo et al.
Journal of Medical Genetics
Congenital Diaphragmatic Hernia Studies
article

The SINEs were there: identification of a pathogenic Alu insertion in a patient with DICER1-related tumour predisposition

Hood Mugalaasi, Mikel Valganon-Petrizan, Helen Hanson, Oluwatosin Taiwo, Avgi Andreou, Henry Cope, Céline Domecq, Iryna Stasevich, Paola Angelini, William D Foulkes, Suzanne Macmahon, Samuel E D Lawrence, Iman Awadh
article en

Abstract

variants, with no detectable germline variant, complicating the genetic diagnosis.A structural variant (SV) initially detected in a tumour sample prompted retrospective review of alignment data from all previously tested tumour, blood and normal tissue samples. This revealed a consistent SV across all samples. Short-read data suggested the SV was an Alu element insertion within the RNase IIIa domain of DICER1, but read length was insufficient for conclusive characterisation.Subsequent long-read nanopore sequencing confirmed a pathogenic AluY insertion, predicted to disrupt DICER1 function.This case highlights the importance of comprehensive genomic and functional analyses, especially in unresolved cases with strong clinical suspicion. It also demonstrates the value of long-read sequencing in identifying complex variants missed by conventional approaches.

Journal of Medical Genetics
Royal Marsden NHS Foundation Trust (GB), Memorial Sloan Kettering Cancer Center (US), University of Exeter (GB), Royal Devon & Exeter NHS Foundation Trust (GB), Great Ormond Street Hospital for Children NHS Foundation Trust (GB), St George’s University Hospitals NHS Foundation Trust (GB), McGill University Health Centre (CA), Genomics England (GB), McGill University (CA)
Royal Marsden NHS Foundation Trust, Canadian Institutes of Health Research
Good health and well-being
Openalex Percentile: Top 35%
Congenital Diaphragmatic Hernia Studies
DOIOpen Access PDFOpenAlex
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