PMM2‐CDG caused by uniparental disomy: Case report and literature review

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 disor...

Descripción completa

Detalles Bibliográficos
Autores principales: Vaes, Laurien, Tiller, George E., Pérez, Belén, Boyer, Suzanne W., Berry, Susan A., Sarafoglou, Kyriakie, Morava, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358672/
https://www.ncbi.nlm.nih.gov/pubmed/32685345
http://dx.doi.org/10.1002/jmd2.12122
_version_ 1783558890575626240
author Vaes, Laurien
Tiller, George E.
Pérez, Belén
Boyer, Suzanne W.
Berry, Susan A.
Sarafoglou, Kyriakie
Morava, Eva
author_facet Vaes, Laurien
Tiller, George E.
Pérez, Belén
Boyer, Suzanne W.
Berry, Susan A.
Sarafoglou, Kyriakie
Morava, Eva
author_sort Vaes, Laurien
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7358672
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley & Sons, Inc.
record_format MEDLINE/PubMed
spelling pubmed-73586722020-07-17 PMM2‐CDG caused by uniparental disomy: Case report and literature review Vaes, Laurien Tiller, George E. Pérez, Belén Boyer, Suzanne W. Berry, Susan A. Sarafoglou, Kyriakie Morava, Eva JIMD Rep Case Reports 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. John Wiley & Sons, Inc. 2020-04-28 /pmc/articles/PMC7358672/ /pubmed/32685345 http://dx.doi.org/10.1002/jmd2.12122 Text en © 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Reports
Vaes, Laurien
Tiller, George E.
Pérez, Belén
Boyer, Suzanne W.
Berry, Susan A.
Sarafoglou, Kyriakie
Morava, Eva
PMM2‐CDG caused by uniparental disomy: Case report and literature review
title PMM2‐CDG caused by uniparental disomy: Case report and literature review
title_full PMM2‐CDG caused by uniparental disomy: Case report and literature review
title_fullStr PMM2‐CDG caused by uniparental disomy: Case report and literature review
title_full_unstemmed PMM2‐CDG caused by uniparental disomy: Case report and literature review
title_short PMM2‐CDG caused by uniparental disomy: Case report and literature review
title_sort pmm2‐cdg caused by uniparental disomy: case report and literature review
topic Case Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358672/
https://www.ncbi.nlm.nih.gov/pubmed/32685345
http://dx.doi.org/10.1002/jmd2.12122
work_keys_str_mv AT vaeslaurien pmm2cdgcausedbyuniparentaldisomycasereportandliteraturereview
AT tillergeorgee pmm2cdgcausedbyuniparentaldisomycasereportandliteraturereview
AT perezbelen pmm2cdgcausedbyuniparentaldisomycasereportandliteraturereview
AT boyersuzannew pmm2cdgcausedbyuniparentaldisomycasereportandliteraturereview
AT berrysusana pmm2cdgcausedbyuniparentaldisomycasereportandliteraturereview
AT sarafogloukyriakie pmm2cdgcausedbyuniparentaldisomycasereportandliteraturereview
AT moravaeva pmm2cdgcausedbyuniparentaldisomycasereportandliteraturereview