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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2020
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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 |
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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 |
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