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

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

doi:10.1016/j.ymgmr.2014.04.003

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

Mol Genet Metab Rep. 2014 Apr 25:1:203-212. doi: 10.1016/j.ymgmr.2014.04.003. eCollection 2014.

Authors

D Bahena-Bahena¹, J López-Valdez², K Raymond³, R Salinas-Marín¹, A Ortega-García¹, B G Ng⁴, H H Freeze⁴, M Ruíz-García⁵, I Martínez-Duncker¹

Affiliations

¹ Human Glycobiology Laboratory, Science Faculty, Morelos State Autonomous University, Cuernavaca, Mexico.
² Department of Genetics, Centenario Miguel Hidalgo Hospital, Aguascalientes, Mexico.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, USA.
⁴ Sanford Burnham Medical Research Institute, La Jolla, USA.
⁵ Neurology Department, National Institute of Pediatrics, Mexico City, Mexico.

Abstract

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.

Keywords: ARCL; ATP6V0A2; CDG; Glycosylation; Hispanic; Laxa.

Publication types

Case Reports