Original ArticlesA Population-Based Study on Congenital Disorders of Protein N- and Combined with O-Glycosylation Experience in Clinical and Genetic Diagnosis
Section snippets
Methods
The 97 subjects examined were, in general, patients with multisystem disease of unknown etiology being monitored at hospitals in the National Health System in Spain, a country with universal health coverage in Europe. Clinical data (physical examination, clinical course of the disease, complementary studies) were collected by the referring specialists, the majority of whom belonged to the national network for the clinical study of CDG. Clinical description of several patients has been reported
Results
Figure 1 (available at www.jpeds.com) shows the results of the analyses performed and the final diagnostic flowchart developed during the 20-year study period. Table I21, 22, 23, 24, 25, 26, 27, 28, 29, 37, 38, 30 provides the clinical data for all 97 patients, with 18 different disorders of protein N- and combined with O-glycosylation. Following clinical suspicion of CDG and complementary laboratory tests aimed at detecting problems of coagulation (mainly a decrease in antithrombin III
Discussion
Congenital defects of glycosylation are clinically and genetically heterogeneous, which makes their diagnosis difficult. Unfortunately, there are only few CDG in which a treatment can change natural history of disease. This is the case of PGM1-CDG and MPI-CDG, which may, respectively, benefit of early treatment with galactose or mannose or liver transplantation, but also DPAGT1-CDG, ALG2-CDG, and ALG14-CDG, where the myasthenic syndrome can be life-threatening if not treated with
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SRD5A3-CDG: Twins with an intragenic tandem duplication
2022, European Journal of Medical GeneticsAssessing the effects of PMM2 variants on protein stability
2021, Molecular Genetics and MetabolismCitation Excerpt :With the exception of p.(Arg141His), for which homozygosity is incompatible with life, and p.(Leu32Arg) for which no homozygosity has been reported, the other two deleterious variants have been found in homozygosity. In addition, we also selected the polymorphic p.(Glu197Ala) for which the impact on the protein remains poorly understood, although it has been found in patients who also carry a severe deleterious variant such is p.(Arg141His) as the second allele [27,45]. According to Silvaggi and collaborators [28], deleterious variants in PMM2 can affect dimerization, catalytic activity or protein stability in general.
Congenital disorders of glycosylation: Prevalence, incidence and mutational spectrum in the Polish population
2021, Molecular Genetics and Metabolism ReportsCitation Excerpt :The c.95TA > GC, p.Leu32Arg mutation was reported in 12 out of 37 Italian patients, all of them presenting with a mild neurological phenotype (preserved ambulatory ability and autonomy) [16]. Comparing with the study of Perez-Cerda et al. reporting 71 Spanish PMM2-CDG patients gathered during the last 20 years, the frequency of c.710C > T, p.Thr237Arg and c.338C > T, p.Pro113Leu were similar [17]. Regarding the mutational spectrum of PMM2-CDGin the Portugese cohort reported by Quelhas et al., a striking similarity with Spanish population was found [18].
Congenital Disorders of Glycosylation in Portugal—Two Decades of Experience
2021, Journal of PediatricsCitation Excerpt :The patients identified with this integrated approach included 1 ALG1-CDG, 1 ATP6AP1-CDG, 1 ATP2AP2-CDG, 2 ATP6V0A2-CDG, 1 CCDC115-CDG, 1 COG1-CDG, 1 COG4-CDG, 2 DPAGT1-CDG, 4 MAN1B1-CDG, 1 PGM1-CDG, 3 RFT1-CDG, 4 SLC35A2-CDG, and 2 SRD5A3-CDG. We compared the mutational spectrum of CDG found in Portuguese families with the one previously reported in a Spanish cohort.38 Only 8 out of 18 CDG found in Spanish patients are shared by the Portuguese cohort (ALG1-CDG, ATP6V0A2-CDG, DPAGT1-CDG, PGM1-CDG, PMM2-CDG, RTF1-CDG, SLC35A2-CDG, and SRD5A3-CDG), which reveals a high level of genotypic differences between the 2 countries, despite their geographic proximity.
Congenital disorders of N-linked glycosylation
2020, Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease: Volume 1
Funded by the National Plan for I+D+I, financed by the General sub-directorate of Evaluation and Promotion of Health Research and the European Regional Development Fund (PI14/00021, PI11/01096, PI11/01254, PI07/0118, PI04/0791), and the Ministry of Economy, Industry and Competitiveness (IPT-2012-0561-010000). The authors declare no conflicts of interest.