2amy

Structural highlights

Disease

[PMM2_HUMAN] Defects in PMM2 are the cause of congenital disorder of glycosylation type 1A (CDG1A) [MIM:212065]; also known as carbohydrate-deficient glycoprotein syndrome type Ia (CDGS1A) or Jaeken syndrome. Congenital disorders of glycosylation are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins. CDG1A is an autosomal recessive disorder characterized by a severe encephalopathy with axial hypotonia, abnormal eye movement, and pronounced psychomotor retardation, as well as peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa. Patients show a peculiar distribution of subcutaneous fat, nipple retraction, and hypogonadism.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]}

Function

[PMM2_HUMAN] Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, Van Schaftingen E. Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). Nat Genet. 1997 May;16(1):88-92. PMID:9140401 doi:10.1038/ng0597-88
2. ↑ Matthijs G, Schollen E, Van Schaftingen E, Cassiman JJ, Jaeken J. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A. Am J Hum Genet. 1998 Mar;62(3):542-50. PMID:9497260 doi:S0002-9297(07)63834-8
3. ↑ Kjaergaard S, Skovby F, Schwartz M. Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1. Eur J Hum Genet. 1998 Jul-Aug;6(4):331-6. PMID:9781039 doi:10.1038/sj.ejhg.5200194
4. ↑ Kondo I, Mizugishi K, Yoneda Y, Hashimoto T, Kuwajima K, Yuasa I, Shigemoto K, Kuroda Y. Missense mutations in phosphomannomutase 2 gene in two Japanese families with carbohydrate-deficient glycoprotein syndrome type 1. Clin Genet. 1999 Jan;55(1):50-4. PMID:10066032
5. ↑ Kjaergaard S, Skovby F, Schwartz M. Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli. Eur J Hum Genet. 1999 Dec;7(8):884-8. PMID:10602363 doi:10.1038/sj.ejhg.5200398
6. ↑ Vuillaumier-Barrot S, Barnier A, Cuer M, Durand G, Grandchamp B, Seta N. Characterization of the 415G>A (E139K) PMM2 mutation in carbohydrate-deficient glycoprotein syndrome type Ia disrupting a splicing enhancer resulting in exon 5 skipping. Hum Mutat. 1999 Dec;14(6):543-4. PMID:10571956 doi:<543::AID-HUMU17>3.0.CO;2-S 10.1002/(SICI)1098-1004(199912)14:6<543::AID-HUMU17>3.0.CO;2-S
7. ↑ Matthijs G, Schollen E, Bjursell C, Erlandson A, Freeze H, Imtiaz F, Kjaergaard S, Martinsson T, Schwartz M, Seta N, Vuillaumier-Barrot S, Westphal V, Winchester B. Mutations in PMM2 that cause congenital disorders of glycosylation, type Ia (CDG-Ia). Hum Mutat. 2000 Nov;16(5):386-94. PMID:11058895 doi:<386::AID-HUMU2>3.0.CO;2-Y 10.1002/1098-1004(200011)16:5<386::AID-HUMU2>3.0.CO;2-Y
8. ↑ Bjursell C, Erlandson A, Nordling M, Nilsson S, Wahlstrom J, Stibler H, Kristiansson B, Martinsson T. PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families. Hum Mutat. 2000 Nov;16(5):395-400. PMID:11058896 doi:<395::AID-HUMU3>3.0.CO;2-T 10.1002/1098-1004(200011)16:5<395::AID-HUMU3>3.0.CO;2-T
9. ↑ Imtiaz F, Worthington V, Champion M, Beesley C, Charlwood J, Clayton P, Keir G, Mian N, Winchester B. Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type 1. J Inherit Metab Dis. 2000 Mar;23(2):162-74. PMID:10801058
10. ↑ Westphal V, Enns GM, McCracken MF, Freeze HH. Functional analysis of novel mutations in a congenital disorder of glycosylation Ia patient with mixed Asian ancestry. Mol Genet Metab. 2001 May;73(1):71-6. PMID:11350185 doi:10.1006/mgme.2001.3174
11. ↑ Schollen E, Martens K, Geuzens E, Matthijs G. DHPLC analysis as a platform for molecular diagnosis of congenital disorders of glycosylation (CDG). Eur J Hum Genet. 2002 Oct;10(10):643-8. PMID:12357336 doi:10.1038/sj.ejhg.5200858
12. ↑ Le Bizec C, Vuillaumier-Barrot S, Barnier A, Dupre T, Durand G, Seta N. A new insight into PMM2 mutations in the French population. Hum Mutat. 2005 May;25(5):504-5. PMID:15844218 doi:10.1002/humu.9336
13. ↑ Schollen E, Keldermans L, Foulquier F, Briones P, Chabas A, Sanchez-Valverde F, Adamowicz M, Pronicka E, Wevers R, Matthijs G. Characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients. Mol Genet Metab. 2007 Apr;90(4):408-13. Epub 2007 Feb 16. PMID:17307006 doi:S1096-7192(07)00027-3