| *154550 | ||||||||||||||||||||||||||||||||||||||||||
| MANNOSEPHOSPHATE ISOMERASE; MPI | ||||||||||||||||||||||||||||||||||||||||||
| Alternative titles; symbols | ||||||||||||||||||||||||||||||||||||||||||
| PHOSPHOMANNOSE ISOMERASE 1; PMI1; PMI | ||||||||||||||||||||||||||||||||||||||||||
| HGNC Approved Gene Symbol: MPI | ||||||||||||||||||||||||||||||||||||||||||
| Cytogenetic location: 15q24.1 Genomic coordinates (GRCh37): 15:75,182,409 - 75,190,564 (from NCBI) | ||||||||||||||||||||||||||||||||||||||||||
| Gene Phenotype Relationships | ||||||||||||||||||||||||||||||||||||||||||
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| TEXT | ||||||||||||||||||||||||||||||||||||||||||
| Description | ||||||||||||||||||||||||||||||||||||||||||
| Mannosephosphate isomerase (MPI), also known as phosphomannose isomerase (PMI; EC 5.3.1.8), catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives which are required for most glycosylation reactions (Proudfoot et al., 1994). | ||||||||||||||||||||||||||||||||||||||||||
| Cloning | ||||||||||||||||||||||||||||||||||||||||||
| Proudfoot et al. (1994) purified human phosphomannose isomerase from placenta tissue. The authors used sequence information obtained from internal fragments of the protein to design degenerate oligonucleotides which were used to amplify a fragment of the PMI cDNA. Using this fragment to screen a human testis cDNA library, Proudfoot et al. (1994) isolated a full-length PMI cDNA. The PMI gene encodes a predicted 423-amino acid polypeptide. Northern blot analysis detected a single 1.8-kb PMI mRNA in all tissues tested, with the highest levels in heart, brain, and skeletal muscle. Recombinant PMI expressed in E. coli had very similar activity to the native enzyme. | ||||||||||||||||||||||||||||||||||||||||||
| Gene Structure | ||||||||||||||||||||||||||||||||||||||||||
| Schollen et al. (2000) determined that the MPI gene contains 8 exons and spans 5 kb. | ||||||||||||||||||||||||||||||||||||||||||
| Mapping | ||||||||||||||||||||||||||||||||||||||||||
| By human-mouse cell hybridization, Shows (1972) concluded that mannosephosphate isomerase and pyruvate kinase-3 (PK3; 179050) are syntenic. By cell hybridization studies, Van Heyningen et al. (1975) found that the MPI and PK3 loci are on chromosome 15. The murine Mpi gene is located on mouse chromosome 9 in the same linkage group as the gene for the LDL receptor (LDLR; 606945) (Frank et al., 1989), which is on chromosome 19 in the human. Human chromosome 19 carries glucosephosphate isomerase (GPI; 172400). These genes may have had a common evolutionary origin but developed different specificities in the evolutionary lines of the 2 species. | ||||||||||||||||||||||||||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||||||||||||||||||||||||||
| In a patient with carbohydrate-deficient glycoprotein syndrome type Ib (CDG Ib, CDG1B; 602579), Niehues et al. (1998) identified a heterozygous mutation in the MPI gene (154550.0001). Schollen et al. (2000) identified a second mutation (154550.0004) in this patient, confirming compound heterozygosity and autosomal recessive inheritance. The mutation resulted in an unstable transcript and was barely detectable at the mRNA level. The findings emphasized the importance of mutation analysis at the genomic DNA level. In a patient with CDG Ib, Jaeken et al. (1998) identified compound heterozygosity for 2 mutations in the MPI gene (154550.0002, 154550.0003). Schollen et al. (2000) identified 8 different mutations in the MPI gene, including 7 novel mutations, in 7 patients with confirmed phosphomannose isomerase deficiency, including a patient previously reported by Niehues et al. (1998). Vuillaumier-Barrot et al. (2002) found that the protein-losing enteropathy-hepatic fibrosis syndrome described in the Saguenay-Lac-Saint-Jean region of Quebec by Pelletier et al. (1986) is caused by an arg295-to-his mutation in the MPI gene (R295H; 154550.0005), and is therefore a form of CDG Ib. | ||||||||||||||||||||||||||||||||||||||||||
| ALLELIC VARIANTS (Selected Examples): | ||||||||||||||||||||||||||||||||||||||||||
| Table View | ||||||||||||||||||||||||||||||||||||||||||
| .0001 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib | ||||||||||||||||||||||||||||||||||||||||||
| MPI, ARG219GLN [dbSNP:rs104894489] | ||||||||||||||||||||||||||||||||||||||||||
| In a patient with CDG Ib (602579), Niehues et al. (1998) identified a heterozygous 656G-A transition in the MPI gene, resulting in an arg219-to-gln (R219Q) substitution. The patient presented at age 11 months with diarrhea and vomiting, protein-losing enteropathy, recurrent thrombotic episodes, and severe life-threatening gastrointestinal bleeding. There was no psychomotor retardation. Treatment with oral mannose resulted in clinical improvement. The patient was heterozygous for the R219Q mutation, which was inherited from the father. By genome sequencing in the patient previously reported by Niehues et al. (1998), Schollen et al. (2000) identified a 1-bp insertion in exon 3 of the MPI gene (116insC; 154550.0004) on the maternal allele, confirming compound heterozygosity. The mutation resulted in an unstable transcript, barely detectable at the mRNA level. The authors emphasized the importance of mutation analysis at the genomic DNA level. | ||||||||||||||||||||||||||||||||||||||||||
| .0002 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib | ||||||||||||||||||||||||||||||||||||||||||
| MPI, SER102LEU [dbSNP:rs104894494] | ||||||||||||||||||||||||||||||||||||||||||
| In a patient with CDG Ib (602579), Jaeken et al. (1998) identified compound heterozygosity for 2 mutations in the MPI gene: a 304C-T transition resulting in a ser102-to-leu (S102L) substitution, and a 413T-C transition resulting in a met138-to-thr (M138T) substitution (154550.0003). Both mutations involve highly conserved residues and are situated near the active site as determined by x-ray crystallography. | ||||||||||||||||||||||||||||||||||||||||||
| .0003 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib | ||||||||||||||||||||||||||||||||||||||||||
| MPI, MET138THR [dbSNP:rs104894495] | ||||||||||||||||||||||||||||||||||||||||||
| See 154550.0002 and Jaeken et al. (1998). | ||||||||||||||||||||||||||||||||||||||||||
| .0004 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib | ||||||||||||||||||||||||||||||||||||||||||
| MPI, 1-BP INS, 166C | ||||||||||||||||||||||||||||||||||||||||||
| See 154550.0001 and Schollen et al. (2000). | ||||||||||||||||||||||||||||||||||||||||||
| .0005 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ib | ||||||||||||||||||||||||||||||||||||||||||
| MPI, ARG295HIS [dbSNP:rs28928906] | ||||||||||||||||||||||||||||||||||||||||||
| Pelletier et al. (1986) described a fatal syndrome of protein-losing enteropathy and congenital hepatic fibrosis in the Saguenay-Lac-Saint-Jean (SLSJ) region of Quebec. Clinically it resembled CDG Ib (602579), with intractable diarrhea, hypoglycemia, hepatomegaly, vomiting, and malnutrition. For this reason, Vuillaumier-Barrot et al. (2002) studied PMI activity in leukocytes of 3 parents of 2 of the affected Canadian children. All 3 showed partial deficiency of leukocyte PMI activity and were heterozygous for an 884G-A transition in exon 7 of the MPI gene, resulting in an arg295-to-his (R295H) mutation. A patient newly diagnosed with CDG Ib from Nantes in Brittany, France, with the same clinical syndrome was found to be homozygous for the R295H mutation and also for nearby polymorphic markers. An identical variant was found for each marker on at least one chromosome of each of the SLSJ parents, consistent with migration from Brittany to Quebec. | ||||||||||||||||||||||||||||||||||||||||||
| See Also: | ||||||||||||||||||||||||||||||||||||||||||
| Chern and Croce (1975); Chern et al. (1977); McMorris et al. (1973); Ritter et al. (1974); Shows (1973) | ||||||||||||||||||||||||||||||||||||||||||
| REFERENCES | ||||||||||||||||||||||||||||||||||||||||||
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