title: ATP6V0A2 mutations present in two Mexican Mestizo children with an autosomal recessive cutis laxa syndrome type IIA.
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 affectingN-linked andO-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.
authors.affiliation: Human Glycobiology Laboratory, Science Faculty, Morelos State Autonomous University, Cuernavaca, Mexico.
authors.forename: D
authors.initials: D
authors.lastname: Bahena-Bahena
authors.affiliation: Department of Genetics, Centenario Miguel Hidalgo Hospital, Aguascalientes, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: López-Valdez
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, USA.
authors.forename: K
authors.initials: K
authors.lastname: Raymond
authors.affiliation: Human Glycobiology Laboratory, Science Faculty, Morelos State Autonomous University, Cuernavaca, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Salinas-Marín
authors.affiliation: Human Glycobiology Laboratory, Science Faculty, Morelos State Autonomous University, Cuernavaca, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Ortega-García
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Ng
authors.affiliation: Sanford Burnham Medical Research Institute, La Jolla, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Freeze
authors.affiliation: Neurology Department, National Institute of Pediatrics, Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Ruíz-García
authors.affiliation: Human Glycobiology Laboratory, Science Faculty, Morelos State Autonomous University, Cuernavaca, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: Martínez-Duncker
keywords: ARCL; ATP6V0A2; CDG; Glycosylation; Hispanic; Laxa