SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals

Bobby G Ng, Paulina Sosicka, Satish Agadi, Mohammed Almannai, Carlos A Bacino, Rita Barone, Lorenzo D Botto, Jennifer E Burton, Colleen Carlston, Brian Hon-Yin Chung, Julie S Cohen, David Coman, Katrina M Dipple, Naghmeh Dorrani, William B Dobyns, Abdallah F Elias, Leon Epstein, William A Gahl, Domenico Garozzo, Trine Bjørg HammerJaclyn Haven, Delphine Héron, Matthew Herzog, George E Hoganson, Jesse M Hunter, Mahim Jain, Jane Juusola, Shenela Lakhani, Hane Lee, Joy Lee, Katherine Lewis, Nicola Longo, Charles Marques Lourenço, Christopher C Y Mak, Dianalee McKnight, Bryce A Mendelsohn, Cyril Mignot, Ghayda Mirzaa, Wendy Mitchell, Hiltrud Muhle, Stanley F Nelson, Mariusz Olczak, Christina G S Palmer, Arthur Partikian, Marc C Patterson, Tyler M Pierson, Shane C Quinonez, Brigid M Regan, M Elizabeth Ross, Maria J Guillen Sacoto, Fernando Scaglia, Ingrid E Scheffer, Devorah Segal, Nilika Shah Singhal, Pasquale Striano, Luisa Sturiale, Joseph D Symonds, Sha Tang, Eric Vilain, Mary Willis, Lynne A Wolfe, Hui Yang, Shoji Yano, Zöe Powis, Sharon F Suchy, Jill A Rosenfeld, Andrew C Edmondson, Stephanie Grunewald, Hudson H Freeze*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

Sider (fra-til)908-925
Antal sider18
TidsskriftHuman Mutation
Udgave nummer7
StatusUdgivet - jul. 2019

Bibliografisk note

© 2019 Wiley Periodicals, Inc.


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