Glycomics in rare diseases: from diagnosis tomechanism.

Autor: Davids M; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland. Electronic address: mariska.davids@nih.gov., Kane MS; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland; Inova Translational Medicine Institute, Inova Health System, Fairfax, Virginia., Wolfe LA; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland., Toro C; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland., Tifft CJ; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland., Adams D; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland., Li X; Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; The Michael J Palmieri Metabolic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Raihan MA; Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; The Michael J Palmieri Metabolic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., He M; Department of Pathology and Laboratory of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; The Michael J Palmieri Metabolic Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Gahl WA; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland., Boerkoel CF; Department of Medical Genetics, University of British Columbia, Vancouver, Canada., Malicdan MCV; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, Maryland; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, Maryland. Electronic address: malicdanm@mail.nih.gov.
Jazyk: angličtina
Zdroj: Translational research : the journal of laboratory and clinical medicine [Transl Res] 2019 Apr; Vol. 206, pp. 5-17. Date of Electronic Publication: 2018 Oct 23.
DOI: 10.1016/j.trsl.2018.10.005
Abstrakt: The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) studies rare genetic disorders not only to achieve diagnoses, but to understand human biology. To ascertain the contribution of protein glycosylation to rare diseases, the NIH UDP used mass spectrometry to agnostically identify abnormalities of N-linked and O-linked glycans in plasma and free oligosaccharides in the urine of 207 patients. 60% of UDP patients had a glycome profile that deviated from control values in at least 1 fluid. Additional evaluation of the fibroblast glycome in 66 patients with abnormalities in plasma and/or urine revealed a consistent glycome phenotype in 83% of these cases. Many of these patients may have secondary glycosylation defects, since it is unlikely that they all have congenital disorders of glycosylation (CDGs). In fact, whole exome sequencing revealed only a few patients with CDGs, along with several others having disorders indirectly altering glycosylation. In summary, we describe a biochemical phenotyping screen to identify defects in protein glycosylation that can elucidate mechanisms of disease among NIH UDP patients.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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