ATP6V0A2 mutations present in two Mexican Mestizo children with an autosomal recessive cutis laxa syndrome type IIA

• Main Authors: D. Bahena-Bahena, J. López-Valdez, K. Raymond, R. Salinas-Marín, A. Ortega-García, B.G. Ng, H.H. Freeze, M. Ruíz-García, I. Martínez-Duncker
• Format: Article
• Language: English
• Published: Elsevier 2014-01-01
• Series: Molecular Genetics and Metabolism Reports
• Subjects: Laxa; Glycosylation; ATP6V0A2; CDG; ARCL; Hispanic
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214426914000317
• ISSN: 2214-4269

Patients with ARCL-IIA harbor mutations in ATP6V0A2 that codes for an organelle proton pump. The ARCL-IIA syndrome characteristically presents a combined glycosylation defect affecting N-linked and O-linked glycosylations, differentiating it from other cutis laxa syndromes and classifying it as a Congenital Disorder of Glycosylation (ATP6V0A2-CDG). We studied two Mexican Mestizo patients with a clinical phenotype corresponding to an ARCL-IIA syndrome. Both patients presented abnormal transferrin (N-linked) glycosylation but Patient 1 had a normal ApoCIII (O-linked) glycosylation profile. Mutational screening of ATP6V0A2 using cDNA and genomic DNA revealed in Patient 1 a previously reported homozygous nonsense mutation c.187C>T (p.R63X) associated with a novel clinical finding of a VSD. In Patient 2 we found a homozygous c.2293C>T (p.Q765X) mutation that had been previously reported but found that it also altered RNA processing generating a novel transcript not previously identified (r.2176_2293del; p.F726Sfs*10). This is the first report to describe Mestizo patients with molecular diagnosis of ARCL-IIA/ATP6V0A2-CDG and to establish that their mutations are the first to be found in patients from different regions of the world and with different genetic backgrounds.