Title | Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Ng, BG, Buckingham, KJ, Raymond, K, Kircher, M, Turner, EH, He, M, Smith, JD, Eroshkin, A, Szybowska, M, Losfeld, ME, Chong, JX, Kozenko, M, Li, C, Patterson, MC, Gilbert, RD, Nickerson, DA, Shendure, J, Bamshad, MJ, Freeze, HH |
Corporate Authors | University of Washington Center for Mendelian Genomics |
Journal | Am J Hum Genet |
Volume | 92 |
Issue | 4 |
Pagination | 632-6 |
Date Published | 2013 Apr 04 |
ISSN | 1537-6605 |
Keywords | Biological Transport, Case-Control Studies, Child, Child, Preschool, Congenital Disorders of Glycosylation, Exome, Female, Glycosylation, Humans, Male, Monosaccharide Transport Proteins, Mosaicism, Mutation, Spectrometry, Mass, Electrospray Ionization, Transferrin, Uridine Diphosphate Galactose |
Abstract | Biochemical analysis and whole-exome sequencing identified mutations in the Golgi-localized UDP-galactose transporter SLC35A2 that define an undiagnosed X-linked congenital disorder of glycosylation (CDG) in three unrelated families. Each mutation reduced UDP-galactose transport, leading to galactose-deficient glycoproteins. Two affected males were somatic mosaics, suggesting that a wild-type SLC35A2 allele may be required for survival. In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement. This may indicate selection against cells carrying the mutant allele. To detect other individuals with such mutations, we suggest transferrin testing in infancy. Here, we report somatic mosaicism in CDG, and our work stresses the importance of combining both genetic and biochemical diagnoses. |
DOI | 10.1016/j.ajhg.2013.03.012 |
Alternate Journal | Am. J. Hum. Genet. |
PubMed ID | 23561849 |
PubMed Central ID | PMC3617373 |
Grant List | U54 HG006493 / HG / NHGRI NIH HHS / United States R01 DK055615 / DK / NIDDK NIH HHS / United States R01DK55615 / DK / NIDDK NIH HHS / United States UM1 HG006493 / HG / NHGRI NIH HHS / United States 1U54HG006493 / HG / NHGRI NIH HHS / United States |