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SLC35A2‐CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals
Author(s) -
Ng Bobby G.,
Sosicka Paulina,
Agadi Satish,
Almannai Mohammed,
Bacino Carlos A.,
Barone Rita,
Botto Lorenzo D.,
Burton Jennifer E.,
Carlston Colleen,
Chung Brian HonYin,
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.,
Quiz 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,
Powis Zöe,
Suchy Sharon F.,
Rosenfeld Jill A.,
Edmondson Andrew C.,
Grunewald Stephanie,
Freeze Hudson H.
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23731
Subject(s) - salt lake , medical genetics , medical school , library science , medicine , gerontology , biology , genetics , medical education , gene , paleontology , structural basin , computer science
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.