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Clinical and molecular diagnosis of non‐phosphomannomutase 2 N‐linked congenital disorders of glycosylation in Spain
Author(s) -
Medrano Celia,
Vega Ana,
Navarrete Rosa,
Ecay M. Jesús,
Calvo Rocío,
Pascual Samuel Ignacio,
RuizPons Mónica,
Toledo Laura,
GarcíaJiménez Inmaculada,
Arroyo Ignacio,
Campo Andrea,
Couce M. Luz,
DomingoJiménez M. Rosario,
GarcíaSilva M. Teresa,
GonzálezGutiérrezSolana Luis,
Hierro Loreto,
MartínHernández Elena,
MartínezPardo Mercedes,
Roldán Susana,
Tomás Miguel,
Cabrera Jose C.,
MártinezBugallo Francisco,
MartínViota Lucía,
VitoriaMiñana Isidro,
Lefeber Dirk J.,
Girós M. Luisa,
Serrano Gimare Mercedes,
Ugarte Magdalena,
Pérez Belén,
PérezCerdá Celia
Publication year - 2019
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13508
Subject(s) - hypotonia , glycosylation , glycan , glycoprotein , biology , psychomotor retardation , genetics , bioinformatics , medicine , pathology , alternative medicine
The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems, but non‐specific symptoms render the diagnosis of the different CDG very challenging. Phosphomannomutase 2 (PMM2)‐CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non‐PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile, 18 were classified as CDG‐I and 7 as CDG‐II. Pathogenic variations were found in 16 genes ( ALG1 , ALG6 , ATP6V0A2 , B4GALT1 , CCDC115 , COG7 , DOLK , DPAGT1 , DPM1 , GFPT1 , MPI , PGM1 , RFT1 , SLC35A2 , SRD5A3 , and SSR4 ). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.