Severe ALG8-CDG (CDG-Ih) associated with homozygosity for two novel missense mutations detected by exome sequencing of candidate genes

European Journal of Medical Genetics

Volumn 55, Issue 3, 2012, Pages 196-202

  Sorte, Hanne ^a   Mørkrid, Lars ^a   Rødningen, Olaug ^a   Kulseth, Mari Ann ^a   Stray Pedersen, Asbjørg ^a   Matthijs, Gert ^b   Race, Valerie ^b   Houge, Gunnar ^c   Fiskerstrand, Torunn ^c   Bjurulf, Bjørn ^a   Lyle, Robert ^a   Prescott, Trine ^a  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c HAUKELAND UNIVERSITY HOSPITAL   (Norway)

Author keywords

ALG8; ALG8 CDG; CDG Ih; Congenital disorder of glycosylation; Exome sequencing

Indexed keywords

ALPHA 1,3 GLUCOSYLTRANSFERASE; DOLICHOL PHOSPHATE; GLUCOSYLTRANSFERASE; NUCLEOTIDE; TRANSFERRIN; UNCLASSIFIED DRUG;

ALG8 GENE; ARTICLE; CASE REPORT; CONGENITAL DISORDER OF GLYCOSYLATION TYPE 1; CONSANGUINEOUS MARRIAGE; DEVELOPMENTAL DISORDER; ELECTROPHORESIS; ENZYME ANALYSIS; EXOME; EXON; FACE DYSMORPHIA; FEMALE; GENE; GENE SEQUENCE; GROWTH RETARDATION; HOMOZYGOSITY; HUMAN; MISSENSE MUTATION; TRANSFERRIN BLOOD LEVEL; VISUAL IMPAIRMENT;

AMINO ACID SEQUENCE; CARBOHYDRATE METABOLISM, INBORN ERRORS; EXOME; FEMALE; GLUCOSYLTRANSFERASES; GLYCOSYLATION; HOMOZYGOTE; HUMANS; INFANT; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; SEQUENCE ANALYSIS, DNA;

EID: 84858862953     PISSN: 17697212     EISSN: 18780849     Source Type: Journal    
DOI: 10.1016/j.ejmg.2012.01.003     Document Type: Article

References (24)

1. Jaeken J. Congenital disorders of glycosylation. Ann. NY Acad. Sci. 2010, 1214:190-198.
2. Jaeken J., Matthijs G. Congenital disorders of glycosylation: a rapidly expanding disease family. Annu. Rev. Genomics Hum. Genet. 2007, 8:261-278.
3. Jaeken J., et al. Sialic acid-deficient serum and cerebrospinal fluid transferrin in a newly recognized genetic syndrome. Clin. Chim. Acta 1984, 144(2-3):245-247.
4. Jaeken J., et al. Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG-deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome?. Pediatr. Res. 1980, 14(2):179.
5. Grünewald S., Matthijs G., Jaeken J. Congenital disorders of glycosylation: a review. Pediatr. Res. 2002, 52(5):618-624.
6. Freeze H.H. Genetic defects in the human glycome. Nat. Rev. Genet. 2006, 7(7):537-551.
7. Haeuptle M.A., Hennet T. Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. Hum. Mutat. 2009, 30(12):1628-1641.
8. Sparks S.E., Krasnewich D.M. Congenital disorders of glycosylation Overview. GeneReviews at GeneTests: Medical Genetics Information Resource (database online) 1997-2011, University of Washington, Seattle, Avaliable at:, [cited 2011 April]. http://www.genetests.org.
9. Thiel C., Korner C. Mouse models for congenital disorders of glycosylation. J. Inherit. Metab. Dis. 2011, 34(4):879-889.
10. Jaeken J., Matthijs G. Congenital disorders of glycosylation. Annu. Rev. Genomics Hum. Genet. 2001, 2:129-151.
11. Westphal V., et al. A frequent mild mutation in ALG6 may exacerbate the clinical severity of patients with congenital disorder of glycosylation Ia (CDG-Ia) caused by phosphomannomutase deficiency. Hum. Mol. Genet. 2002, 11(5):599-604.
12. Harms H.K., et al. Oral mannose therapy persistently corrects the severe clinical symptoms and biochemical abnormalities of phosphomannose isomerase deficiency. Acta Paediatr. 2002, 91(10):1065-1072.
13. de Lonlay P., Seta N. The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation of mannose treatment for CDG-Ib. Biochim. Biophys. Acta 2009, 1792(9):841-843.
14. Charlwood J., et al. A case of the carbohydrate-deficient glycoprotein syndrome type 1 (CDGS type 1) with normal phosphomannomutase activity. J. Inherit. Metab. Dis. 1997, 20(6):817-826.
15. Chantret I., et al. A deficiency in dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase defines a new subtype of congenital disorders of glycosylation. J. Biol. Chem. 2003, 278(11):9962-9971.
16. Schollen E., et al. Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency). J. Med. Genet. 2004, 41(7):550-556.
17. Stölting T., et al. Novel ALG8 mutations expand the clinical spectrum of congenital disorder of glycosylation type Ih. Mol. Genet. Metab. 2009, 98(3):305-309.
18. Eklund E.A., et al. Congenital disorder of glycosylation (CDG)-Ih patient with a severe hepato-intestinal phenotype and evolving central nervous system pathology. J. Pediatr. 2005, 147(6):847-850.
19. Li H., Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009, 25(14):1754-1760.
20. Robinson J.T., et al. Integrative genomics viewer. Nat. Biotechnol. 2011, 29(1):24-26.
21. Lin X., et al. A comprehensive set of primers designed for the PCR and sequencing of human genes 2005, [cited 2011 Feb]; Available from: http://www.ncbi.nlm.nih.gov/projects/genome/probe/doc/ProjVariantSEQr.shtml.
22. Behm-Ansmant I., et al. mRNA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons. FEBS Lett. 2007, 581(15):2845-2853.
23. Vesela K., et al. A new case of ALG8 deficiency (CDG Ih). J. Inherit. Metab. Dis. 2009.
24. Magyar I., et al. Quantitative sequence analysis of FBN1 premature termination codons provides evidence for incomplete NMD in leukocytes. Hum. Mutat. 2009, 30(9):1355-1364.