Kagami Ogata syndrome: a small deletion refines critical region for imprinting

Kagami–Ogata syndrome is a rare imprinting disorder and its phenotypic overlap with multiple different etiologies hampers diagnosis. Genetic etiologies include paternal uniparental isodisomy (upd(14)pat), maternal allele deletions of differentially methylated regions (DMR) in 14q32.2 or pure primary...

Full description

Saved in:
Bibliographic Details
Published in:Npj genomic medicine 2024-01, Vol.9 (1), p.5-5, Article 5
Main Authors: Kilich, Gonench, Hassey, Kelly, Behrens, Edward M., Falk, Marni, Vanderver, Adeline, Rader, Daniel J., Cahill, Patrick J., Raper, Anna, Zhang, Zhe, Westerfer, Dawn, Jadhav, Tanaya, Conlin, Laura, Izumi, Kosuke, Rajagopalan, Ramakrishnan, Sullivan, Kathleen E.
Format: Article
Language:English
Subjects:
631/208/726
692/700/139/1512
Abdomen
Bioinformatics
Biomedical and Life Sciences
Biomedicine
Bone surgery
Case Report
Case reports
DNA methylation
Edema
Epigenetics
Gene Function
Gene Therapy
Genetic screening
Genetic testing
Genetics
Genomes
Genomic imprinting
Hospitals
Human Genetics
Internal Medicine
Medicine
Ostomy
Pathology
Pediatrics
Rib cage
Scoliosis
Ultrasonic imaging
Whole genome sequencing
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Kagami–Ogata syndrome is a rare imprinting disorder and its phenotypic overlap with multiple different etiologies hampers diagnosis. Genetic etiologies include paternal uniparental isodisomy (upd(14)pat), maternal allele deletions of differentially methylated regions (DMR) in 14q32.2 or pure primary epimutations. We report a patient with Kagami–Ogata syndrome and an atypical diagnostic odyssey with several negative standard-of-care genetic tests followed by epigenetic testing using methylation microarray and a targeted analysis of whole-genome sequencing to reveal a 203 bp deletion involving the MEG3 transcript and MEG3: TSS-DMR. Long-read sequencing enabled the simultaneous detection of the deletion, phasing, and biallelic hypermethylation of the MEG3: TSS-DMR region in a single assay. This case highlights the challenges in the sequential genetic testing paradigm, the utility of long-read sequencing as a single comprehensive diagnostic assay, and the smallest reported deletion causing Kagami–Ogata syndrome allowing important insights into the mechanism of imprinting effects at this locus.
ISSN:2056-7944
2056-7944
DOI:10.1038/s41525-023-00389-2