PMM2‐CDG caused by uniparental disomy: Case report and literature review
Laurien Vaes,
George E. Tiller,
Belén Pérez,
Suzanne W. Boyer,
Susan A. Berry,
Kyriakie Sarafoglou,
Eva Morava
Affiliations
Laurien Vaes
Faculty of Medicine KU Leuven Leuven Belgium
George E. Tiller
Department of Genetics Kaiser Permanente Los Angeles California USA
Belén Pérez
Center of Molecular Biology‐Severo Ochoa University Autonomous of Madrid, La Paz Institute for Health Research, Center for Biomedical Research on Rare Diseases Madrid Spain
Suzanne W. Boyer
Department of Clinical Genomics Mayo Clinic Rochester Minnesota USA
Susan A. Berry
Division of Genetics and Metabolism, Department of Pediatrics University of Minnesota Medical School Minneapolis Minnesota USA
Kyriakie Sarafoglou
Department of Pediatrics University of Minnesota Masonic Children's Hospital Minneapolis Minnesota USA
Eva Morava
Department of Clinical Genomics, and Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA
Abstract 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.
