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 Hammer; Jaclyn 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

doi:10.1002/humu.23731

Back

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

Journal article

Open access

Peer reviewed

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, …

Human mutation, Vol.40(7), pp.908-925

07/2019

DOI: https://doi.org/10.1002/humu.23731

PMID: 30817854

Abstract

Animals

Biopsy

Cells, Cultured

CHO Cells

Congenital Disorders of Glycosylation - genetics

Congenital Disorders of Glycosylation - metabolism

Congenital Disorders of Glycosylation - pathology

Cricetulus

Female

Humans

Male

Monosaccharide Transport Proteins - genetics

Monosaccharide Transport Proteins - metabolism

Mutation

Uridine Diphosphate Galactose - metabolism

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.

Files and links (1)

url

https://doi.org/10.1002/humu.23731View

Published (Version of record) Open

Metrics

1 Record Views

See more details

Details

Title: SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals
Creators - without role: Bobby G Ng - Sanford Burnham Prebys Medical Discovery Institute
Paulina Sosicka - Discovery Institute
Satish Agadi - Baylor College of Medicine
Mohammed Almannai - Baylor College of Medicine
Carlos A Bacino - Baylor College of Medicine
Rita Barone - University of Catania
Lorenzo D Botto - University of Utah
Jennifer E Burton - University of Illinois Urbana-Champaign
Colleen Carlston - University of Utah
Brian Hon-Yin Chung - University of Hong Kong
Julie S Cohen - Kennedy Krieger Institute
David Coman - Queensland Children’s Hospital
Katrina M Dipple - University of Washington
Naghmeh Dorrani - UCLA Health
William B Dobyns - University of Washington
Abdallah F Elias - Shodair Children's Hospital
Leon Epstein - Northwestern University
William A Gahl - National Human Genome Research Institute
Domenico Garozzo - Institute of Polymers, Composites and Biomaterials
Trine Bjørg Hammer - Filadelfia
Jaclyn Haven - Shodair Children's Hospital
Delphine Héron - Sorbonne Université
Matthew Herzog - University of California, Los Angeles
George E Hoganson - Illinois College
Jesse M Hunter - Ambry Genetics
Mahim Jain - Kennedy Krieger Institute
Jane Juusola - GeneDx, Gaithersburg, Maryland
Shenela Lakhani - MIND Research Institute
Hane Lee - University of California, Los Angeles
Joy Lee - Royal Children's Hospital
Katherine Lewis - Queensland Children’s Hospital
Nicola Longo - University of Utah
Charles Marques Lourenço - Estácio
Christopher C Y Mak - Chinese University of Hong Kong
Dianalee McKnight - GeneDx, Gaithersburg, Maryland
Bryce A Mendelsohn - University of California, San Francisco
Cyril Mignot - Sorbonne Université
Ghayda Mirzaa - University of Washington
Wendy Mitchell - University of Southern California
Hiltrud Muhle - Kiel University
Stanley F Nelson - University of California, Los Angeles
Mariusz Olczak - University of Wrocław
Christina G S Palmer - University of California, Los Angeles
Arthur Partikian - University of Southern California
Marc C Patterson - Mayo Clinic in Florida
Tyler M Pierson - Cedars-Sinai Medical Center
Shane C Quinonez - University of Michigan–Ann Arbor
Brigid M Regan - Austin Health
M Elizabeth Ross - Weill Cornell Medicine
Maria J Guillen Sacoto - GeneDx, Gaithersburg, Maryland
Fernando Scaglia - Baylor College of Medicine
Ingrid E Scheffer - Austin Health
Devorah Segal - MIND Research Institute
Nilika Shah Singhal - University of California, San Francisco
Pasquale Striano - University of Genoa
Luisa Sturiale - Institute of Polymers, Composites and Biomaterials
Joseph D Symonds - Queen Elizabeth University Hospital
Sha Tang - Ambry Genetics
Eric Vilain - Children's National
Mary Willis - Naval Medical Center San Diego
Lynne A Wolfe - National Institutes of Health
Hui Yang - GeneDx, Gaithersburg, Maryland
Shoji Yano - LAC+USC Medical Center
Zöe Powis - Ambry Genetics
Sharon F Suchy - Ambry Genetics
Jill A Rosenfeld - GeneDx, Gaithersburg, Maryland
Andrew C Edmondson - Baylor College of Medicine
Stephanie Grunewald - Children's Hospital of Philadelphia
Hudson H Freeze - Great Ormond Street Hospital
Publication Details: Human mutation, Vol.40(7), pp.908-925
Grant note: R01 NS058721 / NINDS NIH HHS R01 DK099551 / NIDDK NIH HHS U01 HG007690 / NHGRI NIH HHS U01 HG007709 / NHGRI NIH HHS 5R01NS050375 / NIH (NINDS) 2016/21/B/NZ5/00144 / National Science Center U01 HG007943 / NHGRI NIH HHS U01 HG007530 / NHGRI NIH HHS U01 HG007708 / NHGRI NIH HHS U01 HG007674 / NHGRI NIH HHS T32 GM008638 / NIGMS NIH HHS The Rocket Fund U54 HD090257 / NICHD NIH HHS U01 HG007703 / NHGRI NIH HHS 1R01NS058721 / NIH (NINDS) R01DK099551 / National Institutes of Health (NIH) U54 NS093793 / NINDS NIH HHS R01 NS050375 / NINDS NIH HHS K08 NS092898 / NINDS NIH HHS U01 TR001395 / NCATS NIH HHS U01 HG007942 / NHGRI NIH HHS U01 HG007672 / NHGRI NIH HHS
Identifiers: 9921654908331
Academic Unit: King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article