SLC35A2-CDG: Functional Characterization, Expanded Molecular, Clinical, and Biochemical Phenotypes of 30 Unreported Individuals.

2019

Ng, Bobby G

Sosicka, Paulina

Agadi, Satish

Almannai, Mohammed

Bacino, Carlos A

Barone, Rita

Botto, Lorenzo D

Burton, Jennifer E

Carlston, Colleen

Chung, Brian Hon-Yin

Cohen, Julie S

Coman, David

Dipple, Katrina M

Dorrani, Naghmeh

Dobyns, William B

Elias, Abdallah F

Epstein, Leon

Gahl, William A

Garozzo, Domenico

Hammer, Trine Bjørg

Haven, Jaclyn

Héron, Delphine

Herzog, Matthew

Hoganson, George E

Hunter, Jesse M

Jain, Mahim

Juusola, Jane

Lakhani, Shenela

Lee, Hane

Lee, Joy

Lewis, Katherine

Longo, Nicola

Lourenço, Charles Marques

Mak, Christopher C Y

McKnight, Dianalee

Mendelsohn, Bryce A

Mignot, Cyril

Mirzaa, Ghayda

Mitchell, Wendy

Muhle, Hiltrud

Nelson, Stanley F

Olczak, Mariusz

Palmer, Christina G S

Partikian, Arthur

Patterson, Marc C

Pierson, Tyler M

Quinonez, Shane C

Regan, Brigid M

Ross, M Elizabeth

Guillen Sacoto, Maria J

Scaglia, Fernando

Scheffer, Ingrid E

Segal, Devorah

Singhal, Nilika Shah

Striano, Pasquale

Sturiale, Luisa

Symonds, Joseph D

Tang, Sha

Vilain, Eric

Willis, Mary

Wolfe, Lynne A

Yang, Hui

Yano, Shoji

Undiagnosed Disease Network, null

Powis, Zöe

Suchy, Sharon F

Rosenfeld, Jill A

Edmondson, Andrew C

Grunewald, Stephanie

Freeze, Hudson H

Congenital Disorders of Glycosylation (CDG)

UDP-galactose

glycoside

nucleotide sugar transporter

Journal Article

0000-0002-3677-1216

0000-0002-2311-2174

0000-0001-6934-6518

0000-0001-6440-8089

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10.1002/humu.23731

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-CDG (formerly CDG-IIm). To date, twenty-nine unique de novo variants from thirty-two 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. This article is protected by copyright. All rights reserved.

link

Human Mutation 2019; 40(7): 908-925

Human Mutation