PMM2-CDG caused by uniparental disomy: Case reportand literature review
Entity
UAM. Departamento de Biología MolecularPublisher
John Wiley & SonsDate
2020-04-28Citation
JIMD Reports 54 (2020): 16-21ISSN
2192-8312 (print)Funded by
We thank the patient described in this case report for all-owing us to share her details, and we thank C. Pérez-Cerdá of the Center of Molecular Biology-Severo Ochoa,Madrid, for her contribution. This work is funded by thegrant titled Frontiers in Congenital Disorders of Glycosylation (1U54NS115198-01) from the National Institute ofNeurological Diseases and Stroke (NINDS) and theNational Center for Advancing Translational Sciences(NCATS), and the Rare Disorders Consortium DiseaseNetwork (E.M. and S.K.)Editor's Version
https://doi.org/10.1002/jmd2.12122Subjects
CDG; Chromosome 16; Congenital disorders of glycosylation; Homozygosity; PMM2-CDG; Uniparental isodisomy,; Whole exome sequencing; Biología y Biomedicina / BiologíaRights
© 2020 The AuthorsAbstract
Background
Phosphomannomutase 2 deficiency (PMM2-CDG) affects glycosylation pathways such as the N-glycosylation pathway, resulting in loss of function of multiple proteins. This disorder causes multisystem involvement with a high variability among patients. PMM2-CDG is an autosomal recessive disorder, which can be caused by inheriting two pathogenic variants, de novo mutations or uniparental disomy.
Case Presentation
Our patient presented with multisystem symptoms at an early age including developmental delay, ataxia, and seizures. No diagnosis was obtained till the age of 31 years, when genetic testing was reinitiated. The patient was diagnosed with a complete maternal mixed hetero/isodisomy of chromosome 16, with a homozygous pathogenic PMM2 variant (p.Phe119Leu) causing PMM2-CDG.
A literature review revealed eight cases of uniparental disomy as an underlying cause of CDG, four of which are PMM2-CDG.
Conclusion
Since the incidence of homozygosity for PMM2 variants is rare, we suggest further investigations for every homozygous PMM2-CDG patient where the segregation does not fit. These investigations include testing for UPD or a deletion in one of the two alleles, as this will have an impact on recurrence risk in genetic counseling
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Google Scholar:Vaes, Laurien
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Tiller, George
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Pérez González, María Belén
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Boyer, Suzanne W.
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Berry, Susan A.
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Sarafoglou, Kyriakie
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Morava, Eva
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