title: Clinical, histological and molecular characteristics of Mexican patients with Fabry disease and significant renal involvement.
abstract: OBJECTIVE
  Fabry's disease (FD) is an X-linked lysosomal disorder caused by a deficiency of the enzyme α-galactosidase A that produces accumulation of glycosphingolipids with clinical abnormalities of skin, eye, kidney, heart, brain, and peripheral nervous system. We undertook this study to describe the molecular characteristics of the first four Mexican patients with diagnosis of FD with significant renal involvement, correlating these molecular characteristics with clinical, pathological and biochemical findings.
  
  
  METHODS
  Genomic DNA from Mexican nonrelated patients with presumptive diagnosis of FD was sequenced by polymerase chain reaction (PCR). DNA sequences were compared against sequences in world data bank gene for alpha-galactosidase A (α-GLA, ENSG00000102393) using the BLAST database.
  
  
  RESULTS
  Three patients were confirmed as having FD by displaying mutations in the α-GLA gene. The mutations found are a substitution (p.L243 F) in patient 1, and a substitution (p.A156 V) in patient 3. These two mutations had been previously reported. The new mutation was in patient 2 who displayed a deletion (c.260delA) changing the open reading frame from codon 86 and a stop codon at the 105th residue of the protein, (instead of 429 AA). The fourth patient had lack of mutations in any of the seven exons of α-GLA or 25 base-pair flanking regions; had mild manifestations with kidney histopathological diagnosis of FD that gave us a final diagnosis of atypical phenotype of FD.
  
  
  CONCLUSIONS
  Although the sample is small, it gives a first idea of the molecular and clinical heterogeneity of FD in a Mexican population.
authors.affiliation: Centro de Investigación Social Avanzada, Querétaro, Mexico; Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York; Universidad Panamericana, México, D.F., Mexico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos-Kuri
authors.affiliation: Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, México, D.F., Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Olvera
authors.affiliation: Department of Genetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, México, D.F., Mexico.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Morales
authors.affiliation: Universidad Panamericana, México, D.F., Mexico.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rodriguez-Espino
authors.affiliation: Department of Transplantation Immunogenetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, México, D.F., Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Lara-Mejía
authors.affiliation: Ophthalmology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, México, D.F., Mexico.
authors.forename: Diana
authors.initials: D
authors.lastname: De Los Ríos
authors.affiliation: Universidad Panamericana, México, D.F., Mexico.
authors.forename: Gregorio T
authors.initials: GT
authors.lastname: Obrador
authors.affiliation: Department of Transplantation Immunogenetics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, México, D.F., Mexico. Electronic address: julgrate@yahoo.com.
authors.forename: Julio
authors.initials: J
authors.lastname: Granados
authors.affiliation: Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, México, D.F., Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D003062:Codon; D005091:Exons; D000795:Fabry Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology; D008297:Male; D008800:Mexico; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D003062:Codon; D000519:alpha-Galactosidase
keywords: Fabry disease; Fabry nephropathy; α-GLA-A enzyme; α-galactosidase A