The evolving genetic landscape of congenital disorders of glycosylation

• Published in: Biochimica et biophysica acta. General subjects Vol. 1865; no. 11; p. 129976
• Main Authors: Wilson, Matthew P., Matthijs, Gert
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2021
• Subjects: Autosomal dominant; Congenital Disorders of Glycosylation; Glycosylation; landscape genetics; multiomics; Next generation sequencing; pathophysiology; sequence analysis; Autosomal dominant; Glycosylation; Congenital Disorders of Glycosylation; Next generation sequencing
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2021.129976

Congenital Disorders of Glycosylation (CDG) are an expanding and complex group of rare genetic disorders caused by defects in the glycosylation of proteins and lipids. The genetic spectrum of CDG is extremely broad with mutations in over 140 genes leading to a wide variety of symptoms ranging from mild to severe and life-threatening. There has been an expansion in the genetic complexity of CDG in recent years. More specifically several examples of alternate phenotypes in recessive forms of CDG and new types of CDG following an autosomal dominant inheritance pattern have been identified. In addition, novel genetic mechanisms such as expansion repeats have been reported and several already known disorders have been classified as CDG as their pathophysiology was better elucidated. Furthermore, we consider the future and outlook of CDG genetics, with a focus on exploration of the non-coding genome using whole genome sequencing, RNA-seq and multi-omics technology. •Alternate phenotypes in monogenic CDG•The emergence of autosomal dominant forms of CDG•The future of the genetic diagnosis of CDG