Alternative titles; symbols
HGNC Approved Gene Symbol: MPDU1
SNOMEDCT: 724096007;
Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38) : 17:7,583,647-7,588,212 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17p13.1 | Congenital disorder of glycosylation, type If | 609180 | Autosomal recessive | 3 |
MPD synthase (DPM1; 603503) catalyzes the synthesis of mannose-P-dolichol (MPD), an essential sugar donor for glycoconjugates and an essential substrate for synthesis of glycosylphosphatidylinositols (GPIs). The Chinese hamster ovary (CHO) Lec15 and Lec35 mutant cells are defective in synthesis and utilization, respectively, of MPD. Using an expression cloning strategy, Ware and Lehrman (1996) isolated SL15 (suppressor of Lec15), which was originally thought to correct the Lec15 phenotype and suppress the Lec35 mutation. In an erratum, the authors stated that correction of the Lec15 phenotype was not certain, but they remained confident that the SL15 cDNA suppressed the Lec35 mutation. Sequence analysis indicated that SL15 encodes a transmembrane protein with cytosolic C and N termini. There was no significant sequence similarity between SL15 and the S. cerevisiae MPD synthase, leading the authors to suggest that SL15 plays a distinct role in MPD synthesis. See also DPM2 (603564).
Mao et al. (1998) identified an umbilical cord blood CD34-positive cell cDNA encoding the human homolog of SL15. The predicted human protein contains 247 amino acids.
By analysis of radiation hybrids, Mao et al. (1998) mapped the human SL15 gene to 17p13.1-p12.
Gross (2014) mapped the MPDU1 gene to chromosome 17p13.1 based on an alignment of the MPDU1 sequence (GenBank AF038961) with the genomic sequence (GRCh37).
In 3 unrelated patients with congenital disorder of glycosylation type If (609180), Schenk et al. (2001) identified mutations in the MPDU1 gene: 2 patients of consanguineous parents were homozygotes (604041.0001 and 604041.0002, respectively) and the other was a compound heterozygote (604041.0003 and 604041.0004).
In a patient with CDG If, Kranz et al. (2001) identified a homozygous point mutation in the MPDU1 gene (604041.0005).
In a patient with congenital disorder of glycosylation type If (CDG1F; 609180), Schenk et al. (2001) identified a homozygous 218G-A transition in the MPDU1 gene, resulting in a gly73-to-glu (G73E) substitution.
In a patient with congenital disorder of glycosylation type If (CDG1F; 609180), Schenk et al. (2001) identified a homozygous 356T-C transition in the MPDU1 gene, resulting in a leu119-to-pro (L119P) substitution.
In a patient with congenital disorder of glycosylation type If (CDG1F; 609180), Schenk et al. (2001) identified compound heterozygosity for mutations in the MPDU1 gene: a 2T-C transition, changing the initiating methionine to threonine (met1 to thr), and a 1-bp deletion (511delC; 604041.0004), resulting in a frameshift. The former was of maternal origin and the latter, paternal.
For discussion of the 1-bp deletion in the MPDU1 gene (511delC) that was found in compound heterozygous state in a patient with congenital disorder of glycosylation type If (CDG1F; 609180) by Schenk et al. (2001), see 604041.0003.
In a patient with congenital disorder of glycosylation type If (CDG1F; 609180), Kranz et al. (2001) identified a homozygous 221T-C transition in the MPDU1 gene, resulting in a leu74-to-ser (L74S) substitution. The parents were not known to be consanguineous, but both families had lived in the same village for generations.
Gross, M. B. Personal Communication. Baltimore, Md. 5/27/2014.
Kranz, C., Denecke, J., Lehrman, M. A., Ray, S., Kienz, P., Kreissel, G., Sagi, D., Peter-Katalinic, J., Freeze, H. H., Schmid, T., Jackowski-Dohrmann, S., Harms, E., Marquardt, T. A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If). J. Clin. Invest. 108: 1613-1619, 2001. [PubMed: 11733556] [Full Text: https://doi.org/10.1172/JCI13635]
Mao, M., Fu, G., Wu, J.-S., Zhang, Q.-H., Zhou, J., Kan, L.-X., Huang, Q.-H., He, K.-L., Gu, B.-W., Han, Z.-G., Shen, Y., Gu, J., Yu, Y.-P., Xu, S.-H., Wang, Y.-X., Chen, S.-J., Chen, Z. Identification of genes expressed in human CD34+ hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning. Proc. Nat. Acad. Sci. 95: 8175-8180, 1998. [PubMed: 9653160] [Full Text: https://doi.org/10.1073/pnas.95.14.8175]
Schenk, B., Imbach, T., Frank, C. G., Grubenmann, C. E., Raymond, G. V., Hurvitz, H., Korn-Lubetzki, I., Revel-Vik, S., Raas-Rotschild, A., Luder, A. S., Jaeken, J., Berger, E. G., Matthijs, G., Hennet, T., Aebi, M. MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If. J. Clin. Invest. 108: 1687-1695, 2001. Note: Erratum: J. Clin. Invest. 111: 925 only, 2003. [PubMed: 11733564] [Full Text: https://doi.org/10.1172/JCI13419]
Ware, F. E., Lehrman, M. A. Expression cloning of a novel suppressor of the Lec15 and Lec35 glycosylation mutations of Chinese hamster ovary cells. J. Biol. Chem. 271: 13935-13938, 1996. Note: Erratum: J. Biol. Chem. 273: 13366 only, 1998. [PubMed: 8663248] [Full Text: https://doi.org/10.1074/jbc.271.24.13935]