Mosaicism of the UDP-Galactose Transporter SLC35A2 Causes a Congenital Disorder of Glycosylation

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• 作者：Bobby G. Ng¹ ; Kati J. Buckingham² ; Kimiyo Raymond³ ; Martin Kircher⁴ ; Emily H. Turner⁴ ; Miao He⁵ ; Joshua D. Smith⁴ ; Alexey Eroshkin¹ ; Marta Szybowska⁶ ; Marie E. Losfeld¹ ; Jessica X. Chong² ; Mariya Kozenko⁶ ; Chumei Li⁶ ; Marc C. Patterson⁷ ; Rodney D. Gilbert⁸ ; Deborah A. Nickerson⁴ ; Jay Shendure⁴ ; Michael J. Bamshad² ; ⁴ ; University of Washington Center for Mendelian Genomics
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：4 April, 2013
• 年：2013
• 卷：92
• 期：4
• 页码：632-636
• 全文大小：404 K

文摘

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.