Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation

Bobby G. Ng; Kati J. Buckingham; Kimiyo Raymond; Martin Kircher; Emily H. Turner; Miao He; Joshua D. Smith; Alexey Eroshkin; Marta Szybowska; Marie E. Losfeld; Jessica X. Chong; Mariya Kozenko; Chumei Li; Marc C. Patterson; Rodney D. Gilbert; Deborah A. Nickerson; Jay Shendure; Michael J. Bamshad; Hudson H. Freeze

doi:10.1016/j.ajhg.2013.03.012

Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation

Bobby G. Ng, Kati J. Buckingham, Kimiyo Raymond, Martin Kircher, Emily H. Turner, Miao He, Joshua D. Smith, Alexey Eroshkin, Marta Szybowska, Marie E. Losfeld, Jessica X. Chong, Mariya Kozenko, Chumei Li, Marc C. Patterson, Rodney D. Gilbert, Deborah A. Nickerson, Jay Shendure, Michael J. Bamshad, Hudson H. Freeze

Neurology

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

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.

Original language	English (US)
Pages (from-to)	632-636
Number of pages	5
Journal	American journal of human genetics
Volume	92
Issue number	4
DOIs	https://doi.org/10.1016/j.ajhg.2013.03.012
State	Published - Apr 4 2013

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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Ng, B. G., Buckingham, K. J., Raymond, K., Kircher, M., Turner, E. H., He, M., Smith, J. D., Eroshkin, A., Szybowska, M., Losfeld, M. E., Chong, J. X., Kozenko, M., Li, C., Patterson, M. C., Gilbert, R. D., Nickerson, D. A., Shendure, J., Bamshad, M. J., & Freeze, H. H. (2013). Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation. American journal of human genetics, 92(4), 632-636. https://doi.org/10.1016/j.ajhg.2013.03.012

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 2013, 'Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation', American journal of human genetics, vol. 92, no. 4, pp. 632-636. https://doi.org/10.1016/j.ajhg.2013.03.012

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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.",

author = "Ng, {Bobby G.} and Buckingham, {Kati J.} and Kimiyo Raymond and Martin Kircher and Turner, {Emily H.} and Miao He and Smith, {Joshua D.} and Alexey Eroshkin and Marta Szybowska and Losfeld, {Marie E.} and Chong, {Jessica X.} and Mariya Kozenko and Chumei Li and Patterson, {Marc C.} and Gilbert, {Rodney D.} and Nickerson, {Deborah A.} and Jay Shendure and Bamshad, {Michael J.} and Freeze, {Hudson H.}",

note = "Funding Information: We thank the families for their participation and support. Our work is supported by the Rocket Fund, the National Institutes of Health (NIH) (R01DK55615 to H.H.F.), and is also supported in part by grants from the NIH and the National Human Genome Research Institute (1U54HG006493 to M.J.B., D.A.N., and J.S.). We thank Stephanie Grunewald and Margaret J. McMillin for their contributions. ",

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doi = "10.1016/j.ajhg.2013.03.012",

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AU - Ng, Bobby G.

AU - Buckingham, Kati J.

AU - Raymond, Kimiyo

AU - Kircher, Martin

AU - Turner, Emily H.

AU - He, Miao

AU - Smith, Joshua D.

AU - Eroshkin, Alexey

AU - Szybowska, Marta

AU - Losfeld, Marie E.

AU - Chong, Jessica X.

AU - Kozenko, Mariya

AU - Li, Chumei

AU - Patterson, Marc C.

AU - Gilbert, Rodney D.

AU - Nickerson, Deborah A.

AU - Shendure, Jay

AU - Bamshad, Michael J.

AU - Freeze, Hudson H.

N1 - Funding Information: We thank the families for their participation and support. Our work is supported by the Rocket Fund, the National Institutes of Health (NIH) (R01DK55615 to H.H.F.), and is also supported in part by grants from the NIH and the National Human Genome Research Institute (1U54HG006493 to M.J.B., D.A.N., and J.S.). We thank Stephanie Grunewald and Margaret J. McMillin for their contributions.

PY - 2013/4/4

Y1 - 2013/4/4

N2 - 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.

AB - 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.

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Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation

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