Clinical and molecular features of congenital disorder of glycosylation in patients with type 1 sialotransferrin pattern and diverse ethnic origins

Enns, Gregory M.; Steiner, Robert D.; Buist, Neil R. M.; Cowan, Charles A.; Leppig, Kathleen A.; McCracken, Marjorie F.; Westphal, Vibeke; Freeze, Hudson H.; O’Brien, John F.; Jaeken, Jacques; Matthijs, Gert; Behera, Sarina K.; Hudgins, Louanne

doi:10.1067/mpd.2002.128658

Cited by 38 publications

(32 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of hepatopathies has been described and taught to doctors who are now becoming aware of the need to perform diagnosis after exclusion of more common diseases such as Wilson disease, GSD, and CDGs [8]. Although CDG incidence has been increasing in Western countries over the last few decades, only a few Asian patients have been reported [9][10][11][12][13][14]. Although an Asian-American child with transferrin IEF with a type 1 sialotransferrin pattern from Black and Korean parents has been reported, this child was not confirmed by testing either via PMM2 mutation analysis or PMM2 enzymatic assay [11].…”

Section: Discussionmentioning

confidence: 97%

“…Although CDG incidence has been increasing in Western countries over the last few decades, only a few Asian patients have been reported [9][10][11][12][13][14]. Although an Asian-American child with transferrin IEF with a type 1 sialotransferrin pattern from Black and Korean parents has been reported, this child was not confirmed by testing either via PMM2 mutation analysis or PMM2 enzymatic assay [11]. To the best of our knowledge, this is the first report of a Korean patient with CDG-Ia, both of whose parents were Korean.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: A congenital disorder of glycosylation mimicking glycogen storage disease

Choi

Woo

Choe

et al. 2015

Clinica Chimica Acta

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: A congenital disorder of glycosylation mimicking glycogen storage disease

Choi

Woo

Choe

et al. 2015

Clinica Chimica Acta

View full text Add to dashboard Cite

“…22 CDG commonly exhibits an unusual subcutaneous fat distribution pattern over the buttocks and the suprapubic area. 20,23 The R141H mutation accounts for 40% of disease alleles in CDG-Ia patients, with a carrier frequency of 1/70 in the general population. Ophthalmic manifestations are frequent in CDG-Ia, with congenital esotropia, delayed visual maturation, and retinitis pigmentosa being the most frequent abnormalities noted.…”

Section: Discussionmentioning

confidence: 99%

Congenital disorder of glycosylation type 1a: Three siblings with a mild neurological phenotype

Coman

McGill

Macdonald

et al. 2007

Journal of Clinical Neuroscience

View full text Add to dashboard Cite

“…PMM2-CDG patient-derived fibroblasts were isolated as described (43–46). HFF-1s and PMM2-CDG fibroblasts were cultured in Dulbecco’s modified Eagle’s medium (DMEM) (Invitrogen) supplemented with 30% fetal bovine serum (FBS) (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2

et al. 2016

Self Cite

View full text Add to dashboard Cite

The most common congenital disorder of glycosylation (CDG), phosphomannomutase 2 (PMM2)-CDG, is caused by mutations in PMM2 that limit availability of mannose precursors required for protein N-glycosylation. The disorder has no therapy and there are no models to test new treatments. We generated compound heterozygous mice with the R137H and F115L mutations in Pmm2 that correspond to the most prevalent alleles found in patients with PMM2-CDG. Many Pmm2R137H/F115L mice died prenatally, while survivors had significantly stunted growth. These animals and cells derived from them showed protein glycosylation deficiencies similar to those found in patients with PMM2-CDG. Growth-related glycoproteins insulin-like growth factor (IGF) 1, IGF binding protein-3 and acid-labile subunit, along with antithrombin III, were all deficient in Pmm2R137H/F115L mice, but their levels in heterozygous mice were comparable to wild-type (WT) littermates. These imbalances, resulting from defective glycosylation, are likely the cause of the stunted growth seen both in our model and in PMM2-CDG patients. Both Pmm2R137H/F115L mouse and PMM2-CDG patient-derived fibroblasts displayed reductions in PMM activity, guanosine diphosphate mannose, lipid-linked oligosaccharide precursor and total cellular protein glycosylation, along with hypoglycosylation of a new endogenous biomarker, glycoprotein 130 (gp130). Over-expression of WT-PMM2 in patient-derived fibroblasts rescued all these defects, showing that restoration of mutant PMM2 activity is a viable therapeutic strategy. This functional mouse model of PMM2-CDG, in vitro assays and identification of the novel gp130 biomarker all shed light on the human disease, and moreover, provide the essential tools to test potential therapeutics for this untreatable disease.

show abstract

Clinical and molecular features of congenital disorder of glycosylation in patients with type 1 sialotransferrin pattern and diverse ethnic origins

Cited by 38 publications

References 25 publications

Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: A congenital disorder of glycosylation mimicking glycogen storage disease

Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: A congenital disorder of glycosylation mimicking glycogen storage disease

Congenital disorder of glycosylation type 1a: Three siblings with a mild neurological phenotype

A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2

Contact Info

Product

Resources

About