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Prior Research

The Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) is working to provide the best integrated clinical care for congenital disorders of glycosylation (CDG) in the nation so that, from the patient's perspective, the services delivered are consistent and coordinated. The following publications reflect the prior research conducted by these partners that laid the foundation for the work of our consortium. 

2019

A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality. Balakrishnan B, Verheijen J, Lupo A, Raymond K, Turgeon C, Yang Y, Carter KL, Whitehead KJ, Kozicz T, Morava E, Lai K. J Inherit Metab Dis. 2019 Sep;42(5):998–1007. doi: 10.1002/jimd.12110. Epub 2019 Jun 21. PMID: 31077402; PMCID: PMC6739163.

International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up. Altassan R, Péanne R, Jaeken J, Barone R, Bidet M, Borgel D, Brasil S, Cassiman D, Cechova A, Coman D, Corral J, Correia J, de la Morena-Barrio ME, de Lonlay P, Dos Reis V, Ferreira CR, Fiumara A, Francisco R, Freeze H, Funke S, Gardeitchik T, Gert M, Girad M, Giros M, Grünewald S, Hernández-Caselles T, Honzik T, Hutter M, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-de-Silva D, Martinez AF, Moravej H, Õunap K, Pascoal C, Pascreau T, Patterson M, Quelhas D, Raymond K, Sarkhail P, Schiff M, Seroczyńska M, Serrano M, Seta N, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Witters P, Zeevaert R, Morava E. J Inherit Metab Dis. 42(1):5–28, 2019. PMID: 30740725.

SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals. Ng BG, Sosicka P, Agadi S, Almannai M, Bacino CA, Barone R, Botto LD, Burton JE, Carlston C, Chung BH, Cohen JS, Coman D, Dipple KM, Dorrani N, Dobyns WB, Elias AF, Epstein L, Gahl WA, Garozzo D, Hammer TB, Haven J, Héron D, Herzog M, Hoganson GE, Hunter JM, Jain M, Juusola J, Lakhani S, Lee H, Lee J, Lewis K, Longo N, Lourenço CM, Mak CCY, McKnight D, Mendelsohn BA, Mignot C, Mirzaa G, Mitchell W, Muhle H, Nelson SF, Olczak M, Palmer CGS, Partikian A, Patterson MC, Pierson TM, Quinonez SC, Regan BM, Ross ME, Guillen Sacoto MJ, Scaglia F, Scheffer IE, Segal D, Singhal NS, Striano P, Sturiale L, Symonds JD, Tang S, Vilain E, Willis M, Wolfe LA, Yang H, Yano S, Powis Z, Suchy SF, Rosenfeld JA, Edmondson AC, Grunewald S, Freeze HH. Hum Mutat. 2019 Jul;40(7):908–925. doi: 10.1002/humu.23731. Epub 2019 Apr 24. PMID: 30817854.

The Metabolic Map into the Pathomechanism and Treatment of PGM1-CDG. Radenkovic S, Bird MJ, Emmerzaal TL, Wong SY, Felgueira C, Stiers KM, Sabbagh L, Himmelreich N, Poschet G, Windmolders P, Verheijen J, Witters P, Altassan R, Honzik T, Eminoglu TF, James PM, Edmondson AC, Hertecant J, Kozicz T, Thiel C, Vermeersch P, Cassiman D, Beamer L, Morava E, Ghesquière B. Am J Hum Genet. 2019 May 2;104(5):835–846. doi: 10.1016/j.ajhg.2019.03.003. Epub 2019 Apr 11. PMID: 30982613; PMCID: PMC6506806.

Therapeutic approaches in Congenital Disorders of Glycosylation (CDG) involving N-linked glycosylation: an update. Verheijen J, Tahata S, Kozicz T, Witters P, Morava E . Genet Med. 2020 Feb;22(2):268–279. doi: 10.1038/s41436-019-0647-2. Epub 2019 Sep 19. PMID: 31534212.

A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation. Ferreira CR, Xia ZJ, Clément A, Parry DA, Davids M, Taylan F, Sharma P, Turgeon CT, Blanco-Sánchez B, Ng BG, Logan CV, Wolfe LA, Solomon BD, Cho MT, Douglas G, Carvalho DR, Bratke H, Haug MG, Phillips JB, Wegner J, Tiemeyer M, Aoki K; Undiagnosed Diseases Network; Scottish Genome Partnership, Nordgren A, Hammarsjö A, Duker AL, Rohena L, Hove HB, Ek J, Adams D, Tifft CJ, Onyekweli T, Weixel T, Macnamara E, Radtke K, Powis Z, Earl D, Gabriel M, Russi AHS, Brick L, Kozenko M, Tham E, Raymond KM, Phillips JA 3rd, Tiller GE, Wilson WG, Hamid R, Malicdan MCV, Nishimura G, Grigelioniene G, Jackson A, Westerfield M, Bober MB, Gahl WA, Freeze HH. Am J Hum Genet. 2018 Oct 4;103(4):553–567. doi: 10.1016/j.ajhg.2018.09.003. PMID: 30290151.

Biallelic B3GALT6 mutations cause spondylodysplastic Ehlers–Danlos syndrome. Tim Van Damme, Xiaomeng Pang, Brecht Guillemyn, Sandrine Gulberti, Delfien Syx, Riet De Rycke, Olivier Kaye, Christine E M de Die-Smulders, Rolph Pfundt, Ariana Kariminejad, Sheela Nampoothiri, Geneviève Pierquin, Saskia Bulk, Austin A Larson, Kathryn C Chatfield, Marleen Simon, Anne Legrand, Marion Gerard, Sofie Symoens, Sylvie Fournel-Gigleux, Fransiska Malfait,. Human Molecular Genetics, Volume 27, Issue 20, 15 October 2018, Pages 3475–3487, doi: 10.1093/hmg/ddy234.

CDG Therapies: From Bench to Bedside. Brasil S, Pascoal C, Francisco R, Marques-da-Silva D, Andreotti G, Videira PA, Morava E, Jaeken J, Dos Reis Ferreira V. Int J Mol Sci. 2018 Apr 27;19(5):1304. doi: 10.3390/ijms19051304. PMID: 29702557; PMCID: PMC5983582.

Congenital Disorders of Glycosylation. Chang IJ, He M, Lam CT. Ann Transl Med. 6(24):477, 2018. PMCID none. PMID: 30740408.

Factor VIII and vWF deficiency in STT3A-CDG. Chang IJ, Byers HM, Ng BG, Merritt JL 2nd, Gilmore R, Shrimal S, Wei W, Zhang Y, Blair AB, Freeze HH, Zhang B, Lam C. J Inherit Metab Dis. 2018 Dec 27. Epub ahead of print. PMID: 30701557.

Mosaicism of the UDP-Galactose Transporter SLC35A2 in a Female Causing a Congenital Disorder of Glycosylation. Westenfield K, Sarafoglou K, Speltz LC, Pierpont EI, Steyermark J, Nascene D, Bower M, Pierpont ME. BMC Medical Genetics 2018 Jun 15;19(1):100.

NGLY1-Related Congenital Disorder of Deglycosylation. Lam C, Wolfe L, Need A, Shashi V, Enns G. GeneReviews. (2018). PMID: 29419975

Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation. Ng BG, Rosenfeld JA, Emrick L, Jain M, Burrage LC, Lee B; Undiagnosed Diseases Network, Craigen WJ, Bearden DR, Graham BH, Freeze HH. Am J Hum Genet. 2018 Dec 6;103(6):1030–1037. doi: 10.1016/j.ajhg.2018.10.021. Epub 2018 Nov 29. PMID: 30503518

The challenge of CDG diagnosis. Francisco R, Marques-da-Silva D, Brasil S, Pascoal C, Dos Reis Ferreira V, Morava E, Jaeken J. Mol Genet Metab. 2019 Jan;126(1):1–5. doi: 10.1016/j.ymgme.2018.11.003. Epub 2018 Nov 9. PMID: 30454869.

Transcriptome and functional analysis in a Drosophila model of NGLY1 deficiency provides insight into therapeutic approaches. Katie G Owings, Joshua B Lowry, Yiling Bi, Matthew Might, Clement Y Chow. Human Molecular Genetics. Volume 27. Issue 6. pages 1055–1066. doi: 10.1093/hmg/ddy026 15 March 2018.

TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of α-dystroglycan and muscular dystrophy. Larson, AA, Baker, PR, Milev, MP et al . Skeletal Muscle 8, 17 (2018). doi: 10.1186/s13395-018-0163-0.

Urine Oligosaccharide Screening by MALDI-TOF for the Identification of NGLY1 Deficiency. Hall PL, Lam C, Alexander JJ, Asif G, Berry GT, Ferreira C, Freeze HH, Gahl WA, Nickander KK, Sharer JD, Watson CM, Wolfe L, Raymond KM. Mol Genet Metab. 124(1): 82–86, 2018. PMID: 29550355.

Abnormal glycosylation in Joubert syndrome type 10. Megan S Kane, PhD, Mariska Davids, Michelle R Bond, Christopher J Adams, Megan E Grout, Ian G Phelps, Diana R O’Day, Jennifer C Dempsey, Xeuli Li, Gretchen Golas, Gilbert Vezina, Meral Gunay-Aygun, John A Hanover, Dan Doherty, Miao He, May Christine V Malicdan, William A Gahl, Cornelius F Boerkoel. Cilia 6(2), Mar 2017. PMCID: PMC5364566.

Congenital Disorders of Glycosylation. Christian Thiel, PhD, Nastassja Himmelreich, PhD, Georg F Hoffmann, MD, and Christian Körner, PhD. IN: Pediatric Endocrinology and Inborn Errors of Metabolism (2017). 2nd Edition. Editor: Kyriakie Sarafoglou. McGraw Hill Companies, New York: 951–982.

Detection of phosphoglucomutase-3 (PGM3) deficiency by lectin-based flow cytometry. Carlson RJ, Bond MR, Hutchins S, Brown Y, Wolfe LA, Lam C, Nelson C, DiMaggio D, Jones N, Rosenzweig SD, Stone KD, Freeman AF, Holland SM, Hanover JA, Milner JD, Lyons JJ. J Allergy Clin Immunol. 140(1): 291–294, 2017. PMID: 28063873.

Oral D-galactose supplementation in PGM1-CDG. Wong SY, Gadomski T, van Scherpenzeel M, Honzik T, Hansikova H, Holmefjord KSB, Mork M, Bowling F, Sykut-Cegielska J, Koch D, Hertecant J, Preston G, Jaeken J, Peeters N, Perez S, Nguyen DD, Crivelly K, Emmerzaal T, Gibson KM, Raymond K, Abu Bakar N, Foulquier F, Poschet G, Ackermann AM, He M, Lefeber DJ, Thiel C, Kozicz T, Morava E. Genet Med. 2017 Nov;19(11):1226–1235. doi: 10.1038/gim.2017.41. Epub 2017 Jun 15. PMID: 28617415; PMCID: PMC5675745.

Prospective Phenotyping of NGLY1-CDDG, the First Congenital Disorder of Deglycosylation. Lam C, Ferreira C, Krasnewich D, Toro C, Latham L, Wadih ZM, Lehky T, Brewer C, Baker EH, Thurm A, Farmer CA, Rosenzweig SD, Lyons JJ, Schreiber JM, Gropman A, Lingala S, Ghany MG, Solomon B, Macnamara E, Davids M, Stratakis CA, Kimonis V, Gahl WA, Wolfe L. Genet Med. 19(2):160–168, 2017. PMID: 27388694.

Repurposing of Proton Pump Inhibitors as First Identified Small Molecule Inhibitors of Endo-β-N-acetylglucosaminidase (ENGase) for the Treatment of Rare NGLY1 Genetic Disease. Yiling Bi, Matthew Might, Hariprasad Vankayalapati and Kuberan Balagurunathan. Bioorganic & Medicinal Chemistry Letters. 5 May 2017.

ALG1-CDG: Clinical and molecular characterization of 39 unremported patients. Ng BG, Shiryaev SA, Rymen D, Eklund EA, Raymond K, Kircher M, Abdenur JE, Alehan F, Alina M, Bamshad MJ, Barone R, Berry GT, Brumbaugh JE, Buckingham KJ, Clarkson K, Cole S, O’Connor S, Cooper GM, Van Coster R, Demmer LA, Diogo L, Fay AJ, Ficicioglu C, Fiumara A, Gahl WA, Ganetzky R, Goel H, Harshman LA, He M, Jaeken J, James PM, Katz D, Keldermans L, Kibaek M, Kornberg AJ, Lachlan K, Lam C, Yaplito-Lee J, Nickerson DA, Peters HL, Race V, Régal L, Rush JS, Rutledge SJ, Shendure J, Souche E, Sparks SE, Trapane P, Sanchez-Valle A, Vilain E, Vøllo A, Waechter CJ, Wang RY, Wolfe LA, Wong DA, Wood T, Yang AC, Matthijs G, Freeze HH. Human Mutation. 37(7): 653–60, 2016. PMID: 26931382.

A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2. Chan B, Clasquin M, Smolen GA, Histen G, Powe J, Chen Y, Lin Z, Lu C, Liu Y, Cang Y, Yan Z, Xia Y, Thompson R, Singleton C, Dorsch M, Silverman L, Su SM, Freeze HH, Jin S. Hum Mol Genet. 2016 Jun 1;25(11):2182–2193. Epub 2016 Apr 5. PMID: 27053713.

A novel N-Tetrasaccharide in patients with congenital disorders of glycosylation, including Asparagine-Linked Glycosylation Protein 1, Phosphomannomutase 2, and Mannose Phosphate Isomerase deficiencies. Zhang Wenyue, James Philip M, Ng Bobby G, Li Xueli, Xia Baoyun, Rong Jiang, Asif Ghazia, Raymond Kimiyo, Jones Melanie A, Hegde Madhuri, Ju Tongzhong, Cummings Richard D, Clarkson Katie, Wood Tim, Boerkoel Cornelius F, Freeze Hudson H, He Miao. Clinical Chemistry 62(1): 208–17, Jan 2016. PMCID: PMC4819965.

A severity score for PGM-1 deficiency. Andersson HC. J Pediatr 2016, Aug, 175:1.

Disruption of Golgi morphology and altered protein glycosylation in PLA2G6-associated neurodegeneration. Davids Mariska, Kane Megan S, He Miao, Wolfe Lynne A, Li Xueli, Raihan Mohd A, Chao Katherine R, Bone William P, Boerkoel Cornelius F, Gahl William A, Toro Camilo. Journal of Medical Genetics 53(3): 180–9, Mar 2016. PMCID: PMC5535303.

Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis and decreased glycosylation precursors. Ng BG, Wolfe LA, Ichikawa M, Markello T, He M, Tifft CJ, Gahl WA, Freeze HH. Human Molecular Genetics 24(11): 3050–7, June 2015.

Expanding the Clinical and Molecular Characteristics of PIGT-CDG, a Disorder of Glycosylphosphatidylinositol Anchors. Lam C, Golas AG, Davids M, Huizing M, Kane MS, Krasnewich DM, Malicdan MCV, Adams DR, Markello TC, Zein WM, Gropman AL, Lodish MB, Stratakis CA, Maric I, Rosenzweig SD, Baker EH, Ferreira CR, Danylchuk NR, Kahler S, Garnica AD, Schaefer GB, Boerkoel CF, Gahl WA, Wolfe LA. Mol Genet Metab. 115(2–3): 128–40, 2015. PMID: 25943031.

Glycosylation Analysis for Congenital Disorders of Glycosylation. Xueli Li, Mohd A Raihan, Francis Jeshira Reynoso, Miao He. Current Protocols in Human Genetics. Wiley, 86(17): 1–17, Jul 2015.

ERCC6 dysfunction presenting as progressive neurological decline with brainhypomyelination. Laila Shehata1*, Dimitre R Simeonov1*, Anja Raams, Lynne Wolfe, Adeline Vanderver,Xueli Li, Yan Huang, Shannon Garner, Cornelius F Boerkoel, Audrey Thurm, Gail EHerman, Cynthia J Tifft, Miao He, Nicolaas GJ Jaspers, William A Gahl. Journal of Medical Genetics 8(5): 2892–900, Nov 2014.

Glycosylation, hypogammaglobulinemia, and resistance to viral infections. Sadat MA1, Moir S, Chun TW, Lusso P, Kaplan G, Wolfe L, Memoli MJ, He M, Vega H, Kim LJ, Huang Y, Hussein N, Nievas E, Mitchell R, Garofalo M, Louie A, Ireland DC, Grunes C, Cimbro R, Patel V, Holzapfel G, Salahuddin D, Bristol T, Adams D, Marciano BE, Hegde M, Li Y, Calvo KR, Stoddard J, Justement JS, Jacques J, Long Priel DA, Murray D, Sun P, Kuhns DB, Boerkoel CF, Chiorini JA, Di Pasquale G, Verthelyi D, Rosenzweig SD. New England Journal of Medicine 370(17): 1615–25, April 2014. PMCID: 4066413.

Sialylation of Thomsen-Friedenreichantigen is a noninvasive blood-based biomarker for GNE myopathy. Leoyklang P, Malicdan MC, Yardeni T, Celeste F,Ciccone C, Li X, Jiang R, Gahl WA, Carrillo-Carrasco N, He M, Huizing M. Biomarkers in Medicine 8(5): 641–652, Jun 2014.

The shifting model in clinical diagnostics: how next-generation sequencing and families are altering the way rare diseases are discovered, studied, and treated. Matthew Might and Matt Wilsey. Genetics in Medicine. 20 March 2014.

Molecular diagnostic testing for congenital disorders of glycosylation (CDG): detection rate for single gene testing and next generation sequencing panel testing. Jones MA, Rhodenizer D, da Silva C, Huff IJ, Keong L, Bean LJ, Coffee B, Collins C, Tanner AK, He M, Hegde MR. Molecular Genetics in Metabolism 110(1–2): 78–85, Sept-Oct 2013.

Oligosaccharide analysis in urine by MALDI-TOF mass spectrometry for the diagnosis of lysosomal storage diseases. Xia B, Asif G, Arthur L, Pervaiz MA, Li X, Liu R, Cummings RD, He M. Clinical Chemistry 59(9): 1357–68, Sept 2013.

rhIGF-1 therapy for growth failure and IGF-1 deficiency in Congenital Disorder of Glycosylation Ia (PMM2 deficiency). Miller BS, Duffy MM, Addo OY, Sarafoglou K. Journal of Investigative Medicine High Impact Case Reports. 1:1–4, 2013. doi: 10.1177/2324709613503316. Accepted 7/19/13. Published online: 9/5/13. PMID: 26425584.

Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation. Baoyun Xia, Wenyue Zhang, Xueli Li, Rong Jiang, Tisa Harper, Renpeng Liu, Richard D Cummings, Miao He. Analytical Biochemistry 442(2): 178–85, Nov 2013.

Heritable disorders in the metabolism of the dolichols: A bridge from sterol biosynthesis to molecular glycosylation. Wolfe LA, Morava E, He M, Vockley J, Gibson KM. Am J Med Genet C Semin Med Genet. 160C: 322–8.

Pubertal Development in ALG6 Deficiency (Congenital Disorder of Glycosylation Type Ic). Miller BS, Freeze HH, Hoffmann G, Sarafoglou K. Molecular Genetics and Metabolism 103(1): 101–103, 2011. PMID: 21334936.

The Insulin-like Growth Factor System in Children with Congenital Disorders of Glycosylation. Miller, BS, Khosravi, MJ, Patterson, MC and CA Conover. Miller, B.S., Khosravi, M.J., Patterson, M.C. and C.A. Conover. The Insulin-like Growth Factor System in Children with Congenital Disorders of Glycosylation. Clinical Endocrinology 70:892–7, 2009. PMID: 19207313.

New Disorders in Carbohydrate Metabolism: Congenital Disorders of Glycosylation and their Impact on the Endocrine System. Miller, BS and HH Freeze. Rev Endo Metab Dis 4:1303–13, 2003. PMID: 12618564.

Severe hypoglycemia as a presenting symptom of carbohydrate-deficient glycoprotein syndrome. Babovic-Vuksanovic D, Patterson MC, Schwenk WF, O’Brien JF, Vockley J, Freeze HH, Mehta DP, Michels VV. Journal of Pediatrics. 1999; 135: 775–81.