title: Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects.
abstract: BACKGROUND
  Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations.
  
  
  OBJECTIVE
  We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods  We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives.
  
  
  RESULTS
  We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively.
  
  
  CONCLUSIONS
  The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population.
authors.affiliation: Department of Dermatology, Faculty of Medicine, Complejo Hospitalario Universitario, SERGAS, 15782 Santiago de Compostela, Spain. ladrizos@hotmail.com
authors.forename: L
authors.initials: L
authors.lastname: Rodríguez-Pazos
authors.forename: M
authors.initials: M
authors.lastname: Ginarte
authors.forename: L
authors.initials: L
authors.lastname: Fachal
authors.forename: J
authors.initials: J
authors.lastname: Toribio
authors.forename: A
authors.initials: A
authors.lastname: Carracedo
authors.forename: A
authors.initials: A
authors.lastname: Vega
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006720:Homozygote; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000208:ethnology / Q000235:genetics*; D008084:Lipoxygenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics; D013030:Spain / Q000208:ethnology; D011503:Transglutaminases / Q000235:genetics
chemical_list: C499859:NIPAL4 protein, human; D011956:Receptors, Cell Surface; D003577:Cytochrome P-450 Enzyme System; C559989:CYP4F22 protein, human; C511051:ALOXE3 protein, human; D008084:Lipoxygenase; C514086:ALOX12B protein, human; D001092:Arachidonate 12-Lipoxygenase; D011503:Transglutaminases; C105804:transglutaminase 1