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Int J Mol Sci. 2018 Jul 30;19(8). pii: E2218. doi: 10.3390/ijms19082218.

The Analysis of Variants in the General Population Reveals That PMM2 Is Extremely Tolerant to Missense Mutations and That Diagnosis of PMM2-CDG Can Benefit from the Identification of Modifiers.

Author information

1
Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy. vale.ctr@gmail.com.
2
Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy. chiaracimmaruta@yahoo.it.
3
Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy. maria.monticelli@yahoo.com.
4
Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy. gugli.riccio@libero.it.
5
Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy. arfalas@gmail.com.
6
Dipartimento di Scienze Agrarie ed Agroalimentari, Università Federico II, 80055 Napoli, Italy. arfalas@gmail.com.
7
Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy. cubellis@unina.it.
8
Istituto di Chimica Biomolecolare-CNR, 80078 Pozzuoli, Italy. gandreotti@icb.cnr.it.

Abstract

Type I disorders of glycosylation (CDG), the most frequent of which is phosphomannomutase 2 (PMM2-CDG), are a group of diseases causing the incomplete N-glycosylation of proteins. PMM2-CDG is an autosomal recessive disease with a large phenotypic spectrum, and is associated with mutations in the PMM2 gene. The biochemical analysis of mutants does not allow a precise genotype⁻phenotype correlation for PMM2-CDG. PMM2 is very tolerant to missense and loss of function mutations, suggesting that a partial deficiency of activity might be beneficial under certain circumstances. The patient phenotype might be influenced by variants in other genes associated with the type I disorders of glycosylation in the general population.

KEYWORDS:

clinical informatics; disorder of glycosylation; modifier genes; variant analysis

PMID:
30061496
PMCID:
PMC6121245
DOI:
10.3390/ijms19082218
[Indexed for MEDLINE]
Free PMC Article

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