| *608103 | ||||||||||||
| ALG8, S. CEREVISIAE, HOMOLOG OF | ||||||||||||
| Alternative titles; symbols | ||||||||||||
| ALG8 DOLICHYL-P-GLUCOSE:Glc-1-Man-9-GlcNAc-2-PP-DOLICHYL-ALPHA-3-GLUCOSYLTRANSFERASE | ||||||||||||
| HGNC Approved Gene Symbol: ALG8 | ||||||||||||
| Cytogenetic location: 11q14.1 Genomic coordinates (GRCh37): 11:77,811,987 - 77,850,698 (from NCBI) | ||||||||||||
| Gene Phenotype Relationships | ||||||||||||
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| TEXT | ||||||||||||
| Description | ||||||||||||
| The alpha-3-glucosyltransferase ALG8 adds the second glucose to the lipid-linked oligosaccharide precursor used in the N-glycosylation of proteins. | ||||||||||||
| Cloning | ||||||||||||
| By searching an EST database for human homologs of yeast genes, Stanchi et al. (2001) identified ALG8. They obtained the full-length cDNA and determined that the ALG8 protein contains 532 amino acids. It shares 38% amino acid identity with yeast ALG8. By database analysis, Oriol et al. (2002) identified ALG8. They determined that the 526-amino acid protein has 12 transmembrane domains and an endoplasmic reticulum retention signal (KTKKQ). | ||||||||||||
| Gene Structure | ||||||||||||
| Chantret et al. (2003) determined that the ALG8 gene contains 13 exons. | ||||||||||||
| Mapping | ||||||||||||
| By radiation hybrid analysis, Stanchi et al. (2001) mapped the ALG8 gene to chromosome 11pter-p15.5. However, Chantret et al. (2003) mapped the ALG8 gene to chromosome 11q14 by genomic sequence analysis. | ||||||||||||
| Molecular Genetics | ||||||||||||
| In a patient with congenital disorder of glycosylation Ih (608104), Chantret et al. (2003) identified compound heterozygosity for 2 frameshift mutations (608103.0001-608103.0002) in exon 4 of the ALG8 gene. Schollen et al. (2004) described 3 patients from 2 families with congenital disorder of glycosylation Ih associated with a severe clinical phenotype and early infant death. In each family they identified compound heterozygosity for a splice site mutation and a missense mutation (see 608103.0003 and 608103.0005). Each parent was a carrier of one of the respective mutations. | ||||||||||||
| ALLELIC VARIANTS (Selected Examples): | ||||||||||||
| Table View | ||||||||||||
| .0001 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ih | ||||||||||||
| ALG8, 1-BP DEL, 413C | ||||||||||||
| In a patient with congenital disorder of glycosylation Ih (CDG1H, 608104), Chantret et al. (2003) identified compound heterozygosity for 2 mutations in exon 4 of the ALG8 gene, a 1-bp deletion (413delC) inherited from the father and a 1-bp insertion (396insA; 608103.0002) inherited from the mother. Both mutations gave rise to premature stop codons predicted to generate severely truncated proteins. Because the translation inhibitor emetine stabilized the ALG8 mRNA from the patient to normal levels, it was considered likely that both transcripts underwent nonsense-mediated mRNA decay. The cells from the patient were successfully complemented with wildtype ALG8 cDNA. | ||||||||||||
| .0002 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ih | ||||||||||||
| ALG8, 1-BP INS, 396A | ||||||||||||
| See (608103.0001) and Chantret et al. (2003). | ||||||||||||
| .0003 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ih | ||||||||||||
| ALG8, IVS1AS, A-G, -2 | ||||||||||||
| In a brother and sister with congenital disorder of glycosylation Ih (608104), Schollen et al. (2004) identified compound heterozygosity for an A-to-G transition at position -2 of intron 1 and a 139A-C transversion in exon 2. The splice site mutation causes use of a cryptic splice site, resulting in an 11-bp deletion and a premature stop at codon 38; the transversion in exon 2 results in a thr47-to-pro substitution (T47P; 608103.0004). The sibs also carried a 665A-G polymorphism, which results in an asn222-to-ser (N222S) substitution, on the same allele as the missense mutation. The authors noted that these patients had a much more severe presentation than the patient described by Chantret et al. (2003), including antenatal symptoms and early infant death. | ||||||||||||
| .0004 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ih | ||||||||||||
| ALG8, THR47PRO [dbSNP:rs121908293] | ||||||||||||
| See 608103.0003 and Schollen et al. (2004). | ||||||||||||
| .0005 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ih | ||||||||||||
| ALG8, IVS6DS, A-G, +4 | ||||||||||||
| In a male infant with congenital disorder of glycosylation Ih (608104), Schollen et al. (2004) identified compound heterozygosity for an A-to-G transition at position +4 of intron 6 and an 824G-A transition in exon 8, resulting in a gly275-to-asp substitution (G275D; 608103.0006). The patient had multiple dysmorphic features of the head and extremities, bilateral thoracic and pulmonary hypoplasia, cardiac defects, and diffuse renal and hepatic cystic disease as well as hematopoietic abnormalities, and died at 3 months of age after developing dyspnea due to progressive ascites. | ||||||||||||
| .0006 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ih | ||||||||||||
| ALG8, GLY275ASP [dbSNP:rs121908294] | ||||||||||||
| See 608103.0005 and Schollen et al. (2004). | ||||||||||||
| REFERENCES | ||||||||||||
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