title: Fibroblast apoptosis in a patient affected by lamellar ichthyosis.
abstract: BACKGROUND
  Lamellar ichthyosis (LI) is a congenital recessive skin disorder characterized by generalized scaling and hyperkeratosis. The pathology may be caused by mutations in transglutaminase 1 (TGM1) gene that encodes an enzyme critical for terminally differentiating keratinocytes. Because of evidences that transglutaminase enzymes are involved in programmed cell death, we investigated morphological and biochemical apoptotic parameters in cultured skin fibroblasts from a patient with a severe LI and homozygous for the TGM1 R142H mutation.
  
  
  METHODS
  The principle apoptotic signals (mitochondrial membrane potential, analysis of oxygen consumption, DNA fragmentation and Bax/Bcl-2 gene expression) were analyzed in cultured fibroblasts from a LI patient, his mother (TGM1 mutation carrier) and a control subject.
  
  
  RESULTS
  LI fibroblasts showing a reduction of fibronectin expression evidenced a strong inhibition of oxygen consumption, a dramatic drop in the mitochondrial membrane potential (Delta psi(m)), and a higher apoptotic index.
  
  
  CONCLUSIONS
  The present results suggest a possible connection between the alterations in the keratinization process leading to LI and the observed increased fibroblast apoptosis.
authors.affiliation: Laboratory of Human Molecular Biology and Genetics, Catholic University of the Sacred Heart, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tavian
authors.forename: Roberto
authors.initials: R
authors.lastname: Colombo
authors.forename: Francesco
authors.initials: F
authors.lastname: Misiti
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ena
authors.forename: Luca
authors.initials: L
authors.lastname: Ena
authors.forename: Beatrice
authors.initials: B
authors.lastname: Sampaolese
authors.forename: Bruno
authors.initials: B
authors.lastname: Giardina
authors.forename: Maria E
authors.initials: ME
authors.lastname: Clementi
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D019069:Cell Respiration / Q000502:physiology; D019938:Cyclin D1 / Q000096:biosynthesis; D053938:DNA Fragmentation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008969:Molecular Sequence Data; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D011503:Transglutaminases; C105804:transglutaminase 1