1 - Unidade de Bioquímica Genética, Centro de Genética Médica, Centro Hospitalar Universitário do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, ICBAS, UP, Porto, Portugal; Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário do Porto, Porto, Portugal. Electronic address: Este endereço de email está protegido contra piratas. Necessita ativar o JavaScript para o visualizar..
2 - Unit for Multidisciplinary Research in Biomedicine, ICBAS, UP, Porto, Portugal; Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário do Porto, Porto, Portugal.
3 - i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Population Genetics and Evolution Group, Porto, Portugal; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; FCUP-Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal.
4 - Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário do Porto, Porto, Portugal.
5 - Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.
6 - Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal.
7 - Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de S João, Porto, Portugal.
8 - Unidade de Genética Médica, Centro Genética Médica, Centro Hospitalar do Porto, Porto, Portugal.
9 - Centro de Neuropediatria e Desenvolvimento, Centro Hospitalar Universitário do Algarve, Faro, Portugal.
10 - Centro de Desenvolvimento da Criança, Centro Hospitalar do Funchal, Funchal, Portugal.
11 - Centro Clínico dos SAMS, Lisboa, Portugal.
12 - Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Sta Maria, CHLN, Lisboa, Portugal.
13 - Unidade de Bioquímica Genética, Centro de Genética Médica, Centro Hospitalar Universitário do Porto, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, ICBAS, UP, Porto, Portugal.
14 - Department of Human Genetics, KU Leuven, Leuven, Belgium.
15 - Center for Metabolic Diseases, KU Leuven, Leuven, Belgium.
- J Pediatr. 2021 Apr;231:148-156. doi: 10.1016/j.jpeds.2020.12.026. Epub 2020 Dec 17.
Resumo:
Objective: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDGs) diagnosed in Portugal over the last 20 years.
Study design: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII isoforms and glycan structures were analyzed. Additional studies included measurement of phosphomannomutase (PMM) activity and analysis of lipid-linked oligosaccharides in fibroblasts. Sanger sequencing and massive parallel sequencing were used to identify causal variants or the affected gene, respectively.
Results: Sixty-three individuals were diagnosed covering 14 distinct CDGs; 43 patients diagnosed postnatally revealed a type 1, 14 a type 2, and 2 a normal pattern on serum transferrin isoelectrofocusing. The latter patients were identified by whole exome sequencing. Nine of them presented also a hypoglycosylation pattern on apolipoprotein CIII isoelectrofocusing, pointing to an associated O-glycosylation defect. Most of the patients (62%) are PMM2-CDG and the remaining carry pathogenic variants in ALG1, ATP6AP1, ATP6AP2, ATP6V0A2, CCDC115, COG1, COG4, DPAGT1, MAN1B1, SLC35A2, SRD5A3, RFT1, or PGM1.
Conclusions: Portuguese patients with CDGs are presented in this report, some of them showing unique clinical phenotypes. Among the 14 genes mutated in Portuguese individuals, 8 are shared with a previously reported Spanish cohort. However, regarding the mutational spectrum of PMM2-CDG, the most frequent CDG, a striking similarity between the 2 populations was found, as only 1 mutated allele found in the Portuguese group has not been reported in Spain.