title: [Alpha-1 antitrypsin deficiency caused by Null mutation].
abstract: BACKGROUND
  Alpha-1 antitrypsin deficiency is a hereditary disease defined at the biological level by a serum alpha-1 antitrypsin level below 11μM/L. The null variants are characterized by undetectable circulating alpha-1 antitrypsin levels. Suspicion of a null variant requires the use of appropriate diagnostic techniques.
  
  
  METHODS
  We report the case of a 33-year old patient presenting with dyspnea on exertion, associated with a moderate airflow obstruction, incompletely reversible. His tobacco use was less than 3pack-years. The thoracic CT-scan showed emphysema. The serum alpha-1 antitrypsin level was collapsed. Phenotyping by isoelectrofocusing on agarose gels did not show any band. The study of the SERPINA1 gene, by PCR-sequence of the II, III, IV and V exons and the flanking intronic sequences, allowed identification of the NullQ0ourém allele in homozygous state. This mutation was found in heterozygous state in both parents of the index case and in one of his brothers. The index case showed a rapid aggravation of the airflow obstruction.
  
  
  CONCLUSIONS
  In the case of a serum alpha-1 antitrypsin deficiency, the analysis of the phenotype of the protein by isoelectrofocusing must be performed as a first-line investigation. The detection of an atypical profile may suggest the presence of deficient alleles other than the PI S and PI Z alleles that can only be characterized by sequencing of the whole SERPINA1 gene. The patients carrying a null mutation have a high risk of severe chronic obstructive pulmonary disease.
authors.affiliation: Département de pneumologie, CHU de Nancy, 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France. Electronic address: j.perrin@chu-nancy.fr.
authors.forename: J
authors.initials: J
authors.lastname: Perrin
authors.affiliation: Laboratoire de biochimie-biologie moléculaire-nutrition-métabolisme, CHU de Nancy, 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.
authors.forename: I
authors.initials: I
authors.lastname: Aimone-Gastin
authors.affiliation: Laboratoire de biochimie et biologie moléculaire (HMNO), centre de biologie pathologie, CHRU de Lille, 2, avenue Oscar-Lambret, 59037 Lille cedex, France; Laboratoire de biochimie et biologie moléculaire, faculté de pharmacie, université de Lille 2, 3, rue du Professeur-Laguesse, 59005 Lille cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Balduyck
authors.affiliation: Département de pneumologie, CHU de Nancy, 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.
authors.forename: M
authors.initials: M
authors.lastname: Mercy
authors.affiliation: Laboratoire de biochimie-biologie moléculaire-nutrition-métabolisme, CHU de Nancy, 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.
authors.forename: P
authors.initials: P
authors.lastname: Filhine-Trésarrieu
authors.affiliation: Laboratoire de biochimie et biologie moléculaire (HMNO), centre de biologie pathologie, CHRU de Lille, 2, avenue Oscar-Lambret, 59037 Lille cedex, France; Laboratoire de bactériologie, faculté de pharmacie, université de Lille 2, 3, rue du Professeur-Laguesse, 59005 Lille cedex, France.
authors.forename: M-F
authors.initials: MF
authors.lastname: Odou
authors.affiliation: Département de pneumologie, CHU de Nancy, 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France; Unité de recherche EA 7298 interactions gènes-risques environnementaux et effets sur la santé (INGRES), 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.
authors.forename: A
authors.initials: A
authors.lastname: Chaouat
authors.affiliation: Département de pneumologie, CHU de Nancy, 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France; Unité de recherche EA 7298 interactions gènes-risques environnementaux et effets sur la santé (INGRES), 5, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.
authors.forename: F
authors.initials: F
authors.lastname: Chabot
mesh_terms: D000328:Adult; D018389:Codon, Nonsense; D004417:Dyspnea / Q000235:genetics; D006801:Humans; D008297:Male; D010641:Phenotype; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics* / Q000473:pathology
chemical_list: D018389:Codon, Nonsense; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin
keywords: Alpha-1 antitrypsin deficiency; Déficit en alpha-1 antitrypsine; Genotyping; Génotypage; Mutation Null; Null mutation; PI phenotype; Phénotype PI; SERPINA1