title: Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation.
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.
authors.affiliation: Genetic Disease Program, Sanford Children's Health Research Center, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: Bobby G
authors.initials: BG
authors.lastname: Ng
authors.forename: Kati J
authors.initials: KJ
authors.lastname: Buckingham
authors.forename: Kimiyo
authors.initials: K
authors.lastname: Raymond
authors.forename: Martin
authors.initials: M
authors.lastname: Kircher
authors.forename: Emily H
authors.initials: EH
authors.lastname: Turner
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Smith
authors.forename: Alexey
authors.initials: A
authors.lastname: Eroshkin
authors.forename: Marta
authors.initials: M
authors.lastname: Szybowska
authors.forename: Marie E
authors.initials: ME
authors.lastname: Losfeld
authors.forename: Jessica X
authors.initials: JX
authors.lastname: Chong
authors.forename: Mariya
authors.initials: M
authors.lastname: Kozenko
authors.forename: Chumei
authors.initials: C
authors.lastname: Li
authors.forename: Marc C
authors.initials: MC
authors.lastname: Patterson
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Gilbert
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bamshad
authors.forename: Hudson H
authors.initials: HH
authors.lastname: Freeze
mesh_terms: D001692:Biological Transport; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D059472:Exome / Q000235:genetics; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D021241:Spectrometry, Mass, Electrospray Ionization; D014168:Transferrin / Q000032:analysis / Q000378:metabolism; D014531:Uridine Diphosphate Galactose / Q000378:metabolism*; D000099237:UDP-Galactose Translocators
chemical_list: D009004:Monosaccharide Transport Proteins; D014168:Transferrin; D014531:Uridine Diphosphate Galactose; D000099237:UDP-Galactose Translocators
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