Identification Through Exome Sequencing of the First PMM2-CDG Individual of Mexican Mestizo Origin

Overview

Journal Mol Genet Metab Rep

Specialty Endocrinology

Date 2020 Sep 3

PMID 32874916

Citations 4

Authors

C A Gonzalez-Dominguez

A Raya-Trigueros

S Manrique-Hernandez

A Gonzalez Jaimes

R Salinas-Marin

C Molina-Garay

K Carrillo-Sanchez

L L Flores-Lagunes

M Jimenez-Olivares

C Dehesa-Caballero

C Alaez-Verson

I Martinez-Duncker

Affiliations

Soon will be listed here.

Abstract

Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in c.422G > A (p.R141H) and c.395 T > C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.

Citing Articles

Characterization of a missense variant in COG5 in a Tunisian patient with COG5-CDG syndrome and insights into the effect of non-synonymous variants on COG5 protein.

Khabou B, Sahari U, Ben Issa A, Bouchaala W, Szenker-Ravi E, Ng A J Hum Genet. 2024; 69(11):591-597.

PMID: 38987656 DOI: 10.1038/s10038-024-01273-2.

-CDG T237M Mutation in a Patient with Cerebral Palsy-Like Phenotypes Reported from South India.

Sreedevi N, Swapna N, Maruthy S, Meghavathi H, Sylvester C Glob Med Genet. 2023; 10(2):105-108.

PMID: 37274081 PMC: 10234699. DOI: 10.1055/s-0043-1769494.

ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele.

Gonzalez-Dominguez C, Fiesco-Roa M, Gomez-Carmona S, Kleinert-Altamirano A, He M, Daniel E Front Genet. 2021; 12:744884.

PMID: 34567092 PMC: 8458739. DOI: 10.3389/fgene.2021.744884.

Non-functional alternative splicing caused by a Latino pathogenic variant in a case of PMM2-CDG.

Gonzalez-Dominguez C, Villarroel C, Rodriguez-Morales M, Manrique-Hernandez S, Gonzalez-Jaimes A, Olvera-Rodriguez F Mol Genet Metab Rep. 2021; 28:100781.

PMID: 34277356 PMC: 8264207. DOI: 10.1016/j.ymgmr.2021.100781.

References

Yildiz Y, Arslan M, Celik G, Kasapkara C, Ceylaner S, Dursun A . Genotypes and estimated prevalence of phosphomannomutase 2 deficiency in Turkey differ significantly from those in Europe. Am J Med Genet A. 2020; 182(4):705-712. DOI: 10.1002/ajmg.a.61488. View

Citro V, Cimmaruta C, Monticelli M, Riccio G, Mele B, Cubellis M . The Analysis of Variants in the General Population Reveals That Is Extremely Tolerant to Missense Mutations and That Diagnosis of PMM2-CDG Can Benefit from the Identification of Modifiers. Int J Mol Sci. 2018; 19(8). PMC: 6121245. DOI: 10.3390/ijms19082218. View

Vuillaumier-Barrot S, Hetet G, Barnier A, Dupre T, Cuer M, de Lonlay P . Identification of four novel PMM2 mutations in congenital disorders of glycosylation (CDG) Ia French patients. J Med Genet. 2000; 37(8):579-80. PMC: 1734666. DOI: 10.1136/jmg.37.8.579. View

Bahena-Bahena D, Lopez-Valdez J, Raymond K, Salinas-Marin R, Ortega-Garcia A, Ng B . ATP6V0A2 mutations present in two Mexican Mestizo children with an autosomal recessive cutis laxa syndrome type IIA. Mol Genet Metab Rep. 2016; 1:203-212. PMC: 5121299. DOI: 10.1016/j.ymgmr.2014.04.003. View

Freeze H, Westphal V . Balancing N-linked glycosylation to avoid disease. Biochimie. 2001; 83(8):791-9. DOI: 10.1016/s0300-9084(01)01292-5. View

Monin M, Mignot C, de Lonlay P, Heron B, Masurel A, Mathieu-Dramard M . 29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype. Orphanet J Rare Dis. 2014; 9:207. PMC: 4266234. DOI: 10.1186/s13023-014-0207-4. View

Carchon H, Van Schaftingen E, Matthijs G, Jaeken J . Carbohydrate-deficient glycoprotein syndrome type IA (phosphomannomutase-deficiency). Biochim Biophys Acta. 1999; 1455(2-3):155-65. DOI: 10.1016/s0925-4439(99)00073-3. View

Matthijs G, Schollen E, Van Schaftingen E, Cassiman J, Jaeken J . Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A. Am J Hum Genet. 1998; 62(3):542-50. PMC: 1376957. DOI: 10.1086/301763. View

Schollen E, Keldermans L, Foulquier F, Briones P, Chabas A, Sanchez-Valverde F . Characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients. Mol Genet Metab. 2007; 90(4):408-13. DOI: 10.1016/j.ymgme.2007.01.003. View

10.

Barone R, Carrozzi M, Parini R, Battini R, Martinelli D, Elia M . A nationwide survey of PMM2-CDG in Italy: high frequency of a mild neurological variant associated with the L32R mutation. J Neurol. 2014; 262(1):154-64. DOI: 10.1007/s00415-014-7549-7. View

11.

Hernandez-Nieto C, Alkon-Meadows T, Lee J, Cacchione T, Iyune-Cojab E, Garza-Galvan M . Expanded carrier screening for preconception reproductive risk assessment: Prevalence of carrier status in a Mexican population. Prenat Diagn. 2020; 40(5):635-643. DOI: 10.1002/pd.5656. View

12.

Chang I, He M, Lam C . Congenital disorders of glycosylation. Ann Transl Med. 2019; 6(24):477. PMC: 6331365. DOI: 10.21037/atm.2018.10.45. View

13.

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; 25(5):504-5. DOI: 10.1002/humu.9336. View

14.

Magalhaes A, Burin M, de Souza C, Bitencourt F, Sebastiao F, Silva T . Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten-year experience in a Brazilian center. J Pediatr (Rio J). 2019; 96(6):710-716. PMC: 9432258. DOI: 10.1016/j.jped.2019.05.008. View

15.

Martinez-Monseny A, Bolasell M, Callejon-Poo L, Cuadras D, Freniche V, Itzep D . AZATAX: Acetazolamide safety and efficacy in cerebellar syndrome in PMM2 congenital disorder of glycosylation (PMM2-CDG). Ann Neurol. 2019; 85(5):740-751. DOI: 10.1002/ana.25457. View

16.

Grunewald S, Schollen E, Van Schaftingen E, Jaeken J, Matthijs G . High residual activity of PMM2 in patients' fibroblasts: possible pitfall in the diagnosis of CDG-Ia (phosphomannomutase deficiency). Am J Hum Genet. 2001; 68(2):347-54. PMC: 1235268. DOI: 10.1086/318199. View

17.

Asteggiano C, Papazoglu M, Bistue Millon M, Peralta M, Azar N, Specola N . Ten years of screening for congenital disorders of glycosylation in Argentina: case studies and pitfalls. Pediatr Res. 2018; 84(6):837-841. DOI: 10.1038/s41390-018-0206-6. View

18.

Altassan R, Peanne R, Jaeken J, Barone R, Bidet M, Borgel D . International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up. J Inherit Metab Dis. 2019; 42(1):5-28. DOI: 10.1002/jimd.12024. View

19.

de Lonlay P, Seta N, Barrot S, Chabrol B, Drouin V, Gabriel B . A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases. J Med Genet. 2001; 38(1):14-9. PMC: 1734729. DOI: 10.1136/jmg.38.1.14. View