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

• Main Authors: C.A. González-Domínguez, C.E. Villarroel, M. Rodríguez-Morales, S. Manrique-Hernández, A. González-Jaimes, F. Olvera-Rodriguez, K. Beutelspacher, C. Molina-Garay, K. Carrillo-Sánchez, L.L. Flores-Lagunes, M. Jiménez-Olivares, A. Muñoz-Rivas, M.E. Cruz-Muñoz, H.M. Mora-Montes, R. Salinas-Marín, C. Alaez-Verson, I. Martínez-Duncker
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Series: Molecular Genetics and Metabolism Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214426921000756

We report on a Mexican mestizo with a multisystemic syndrome including neurological involvement and a type I serum transferrin isoelectric focusing (Tf IEF) pattern. Diagnosis of PMM2-CDG was obtained by clinical exome sequencing (CES) that revealed compound heterozygous variants in PMM2, the encoding gene for the phosphomannomutase 2 (PMM2). This enzyme 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. The identified variants were c.422G>A (R141H) and c.178G>T, the former being the most frequent PMM2 pathogenic mutation and the latter a previously uncharacterized variant restricted to the Latino population with conflicting interpretations of pathogenicity and that we here report causes leaky non-functional alternative splicing (p.V60Cfs*3).