title: Contribution of CYP1B1 mutations and founder effect to primary congenital glaucoma in Mexico.
abstract: OBJECTIVE
  The frequency of primary congenital glaucoma (PCG)-causing CYP1B1 mutations varies importantly among distinct populations, ranging from 20% in Indonesians and Japanese to about 100% among the Saudi Arabians and Slovakian Gypsies. Thus, the molecular characterization of large groups of PCG from different ethnic backgrounds is important to establish the actual CYP1B1 contribution in specific populations. In this work, the molecular analysis of the CYP1B1 gene in a group of Mexican PCG patients is reported.
  
  
  METHODS
  Thirty unrelated Mexican patients fulfilling the clinical criteria for PCG were included. Two cases were familial and with proven consanguinity, originating from distinct regions of the country. Polymerase chain reaction amplification and direct automated sequencing of the CYP1B1 coding region was performed in each participating subject.
  
  
  RESULTS
  An identical pathogenic CYP1B1 mutation was demonstrated in 2 unrelated PCG subjects. The mutation consisted of a homozygous G to A transition at nucleotide position 1505 in exon 3, which predicted a substitution of glutamic acid for lysine at residue 387 of the protein (E387K). In the remaining 28 PCG subjects, no deleterious mutations were identified. Both subjects with the E387K mutation shared a same haplotype for 5 CYP1B1 intragenic single nucleotide polymorphisms, indicating a common origin of the allele.
  
  
  CONCLUSIONS
  Mexican patients with PCG are rarely (less than 10%) due to CYP1B1 mutations. Available data indicate that most of the non-Brazilian Latin American PCG patients investigated to date are not due to CYP1B1 defects. Populations with low incidence of CYP1B1 mutations are appropriate candidates for the identification of novel PCG-causing genes.
authors.affiliation: Department of Genetics-Research Unit, Institute of Ophthalmology Conde de Valenciana, Mexico City, México. jczenteno@institutodeoftalmologia.org
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zenteno
authors.forename: Elena
authors.initials: E
authors.lastname: Hernandez-Merino
authors.forename: Herlinda
authors.initials: H
authors.lastname: Mejia-Lopez
authors.forename: Margarita
authors.initials: M
authors.lastname: Matías-Florentino
authors.forename: Norma
authors.initials: N
authors.lastname: Michel
authors.forename: Celia
authors.initials: C
authors.lastname: Elizondo-Olascoaga
authors.forename: Vincent
authors.initials: V
authors.lastname: Korder-Ortega
authors.forename: Homero
authors.initials: H
authors.lastname: Casab-Rueda
authors.forename: Jose Elias
authors.initials: JE
authors.lastname: Garcia-Ortiz
mesh_terms: D000293:Adolescent; D000328:Adult; D044467:American Indian or Alaska Native / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005901:Glaucoma / Q000151:congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1