Related Experiment Video
Updated: Dec 14, 2025
Microsatellite DNA Genotyping and Flow Cytometry Ploidy Analyses of Formalin-fixed Paraffin-embedded Hydatidiform Molar Tissues
Published on: October 20, 2019
PMM2-CDG caused by uniparental disomy: Case report and literature review
Laurien Vaes1, George E Tiller2, Belén Pérez3
1Faculty of Medicine KU Leuven Leuven Belgium.
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.
Insights
Phosphomannomutase 2 deficiency (PMM2-CDG) is a rare genetic disorder. This case highlights uniparental disomy as a cause of PMM2-CDG, emphasizing the need for further genetic testing in specific cases.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Phosphomannomutase 2 deficiency (PMM2-CDG) disrupts N-glycosylation, impacting protein function and causing multisystemic symptoms with variable presentation.
- It is an autosomal recessive disorder typically caused by inheriting two pathogenic variants, de novo mutations, or uniparental disomy.
Observation:
- A patient presented with early-onset multisystemic symptoms including developmental delay, ataxia, and seizures, remaining undiagnosed until age 31.
- Genetic testing revealed a complete maternal mixed hetero/isodisomy of chromosome 16 and a homozygous pathogenic PMM2 variant (p.Phe119Leu), confirming PMM2-CDG.
Findings:
- This case represents a rare instance of PMM2-CDG caused by uniparental disomy (UPD).
- A literature review identified eight cases of UPD underlying CDG, with four specifically linked to PMM2-CDG.
Implications:
- The rarity of PMM2 variant homozygosity suggests further investigation for UPD or deletions in homozygous PMM2-CDG patients with atypical segregation.
- Identifying UPD is crucial for accurate genetic counseling and determining recurrence risks.
Related Concept Videos
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:21Nondisjunction
01:29Nondisjunction
03:09Meiosis I
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
02:02Meiosis II
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
02:59Animal Mitochondrial Genetics