Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation

Silvia Radenkovic; Taylor Fitzpatrick-Schmidt; Seul Kee Byeon; Anil K Madugundu; Mayank Saraswat; Angie Lichty; Sunnie Y W Wong; Stephen McGee; Katharine Kubiak; Anna Ligezka; Wasantha Ranatunga; Yuebo Zhang; Tim Wood; Michael J Friez; Katie Clarkson; Akhilesh Pandey; Julie R Jones; Eva Morava

doi:10.1016/j.ymgme.2020.10.007

Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation

Mol Genet Metab. 2021 Jan;132(1):27-37. doi: 10.1016/j.ymgme.2020.10.007. Epub 2020 Oct 17.

Authors

Silvia Radenkovic¹, Taylor Fitzpatrick-Schmidt², Seul Kee Byeon³, Anil K Madugundu⁴, Mayank Saraswat⁴, Angie Lichty⁵, Sunnie Y W Wong⁶, Stephen McGee⁵, Katharine Kubiak⁵, Anna Ligezka⁷, Wasantha Ranatunga⁷, Yuebo Zhang⁷, Tim Wood⁵, Michael J Friez⁵, Katie Clarkson⁵, Akhilesh Pandey⁸, Julie R Jones⁵, Eva Morava⁹

Affiliations

¹ Mayo Clinic, Department of Clinical Genomics, Rochester, MN, USA; Metabolomics Expertise Center, CCB, KU Leuven-VIB, Leuven, Belgium; Laboratory of Hepatology, Department of CHROMETA, KU Leuven, Leuven, Belgium. Electronic address: silvia.radenkovic@kuleuven.be.
² Tulane University Medical School, New Orleans, LA, USA.
³ Mayo Clinic, Department of Laboratory of Medical Pathology, Rochester, MN, USA.
⁴ Mayo Clinic, Department of Laboratory of Medical Pathology, Rochester, MN, USA; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India; Manipal Academy of Higher Education, Manipal, Karnataka, India.
⁵ Greenwood Genetic Center, Greenwood, SC, USA.
⁶ Tulane University Medical School, New Orleans, LA, USA; Stanford University, CA, USA.
⁷ Mayo Clinic, Department of Clinical Genomics, Rochester, MN, USA.
⁸ Mayo Clinic, Department of Laboratory of Medical Pathology, Rochester, MN, USA; Mayo Clinic, Center for Individualized Medicine, Rochester, MN, USA.
⁹ Mayo Clinic, Department of Clinical Genomics, Rochester, MN, USA; Mayo Clinic, Department of Laboratory of Medical Pathology, Rochester, MN, USA.

Abstract

Pathogenic alterations in the DPM2 gene have been previously described in patients with hypotonia, progressive muscle weakness, absent psychomotor development, intractable seizures, and early death. We identified biallelic DPM2 variants in a 23-year-old male with truncal hypotonia, hypertonicity, congenital heart defects, intellectual disability, and generalized muscle wasting. His clinical presentation was much less severe than that of the three previously described patients. This is the second report on this ultra-rare disorder. Here we review the characteristics of previously reported individuals with a defect in the DPM complex while expanding the clinical phenotype of DPM2-Congenital Disorders of Glycosylation. In addition, we offer further insights into the pathomechanism of DPM2-CDG disorder by introducing glycomics and lipidomics analysis.

Keywords: CDG; Dolichophosphomannose; Intellectual disability; Lipidomics; Muscle weakness.

Publication types

Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Congenital Disorders of Glycosylation / diagnosis
Congenital Disorders of Glycosylation / genetics*
Congenital Disorders of Glycosylation / pathology
Genetic Predisposition to Disease*
Humans
Intellectual Disability / diagnosis
Intellectual Disability / genetics*
Intellectual Disability / pathology
Male
Mannosyltransferases / genetics*
Muscle Weakness / diagnosis
Muscle Weakness / genetics
Muscle Weakness / pathology
Mutation / genetics
Phenotype

Substances

DPM2 protein, human
Mannosyltransferases

Abstract

Publication types

MeSH terms

Substances

Grants and funding