title: Homozygosity for a factor XII mutation in one female and one male patient with hereditary angio-oedema.
abstract: Hereditary angio-oedema (HAE) with normal C1 inhibitor is associated with heterozygous mutations in the factor XII gene (FXII-HAE). We report two Brazilian FXII-HAE families segregating the mutation c.983 C>A (p.Thr328Lys). In each family, one patient with a homozygous mutation was found. The homozygous female patient in family 1 displayed a severe phenotype. However, this falls within the clinical phenotype spectrum reported for heterozygous female mutation carriers. The homozygous male patient in family 2 also showed a severe phenotype. This finding is intriguing, as to our knowledge, it is the first such report for a male FXII-HAE mutation carrier. In the rare instances in which male mutation carriers are affected, a mild phenotype is typical. The present findings therefore suggest that homozygous FXII-HAE mutation status leads to a severe phenotype in females and males, and to an increased risk of manifest symptoms in the latter.
authors.affiliation: Outpatient Group of Recurrent Infections and Laboratory of Clinical Immunology, Faculty of Medicine ABC, Santo André, Brazil.
authors.forename: A S
authors.initials: AS
authors.lastname: Grumach
authors.affiliation: Department of Genomics, Life & Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.|Center for Rare Diseases Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Stieber
authors.affiliation: Department of Biophysics, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: C L
authors.identifier: http://orcid.org/0000-0001-9565-1911
authors.initials: CL
authors.lastname: Veronez
authors.affiliation: Department of Biophysics, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: N
authors.initials: N
authors.lastname: Cagini
authors.affiliation: Outpatient Group of Recurrent Infections and Laboratory of Clinical Immunology, Faculty of Medicine ABC, Santo André, Brazil.
authors.forename: R N
authors.initials: RN
authors.lastname: Constantino-Silva
authors.affiliation: Outpatient Group of Recurrent Infections and Laboratory of Clinical Immunology, Faculty of Medicine ABC, Santo André, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Cordeiro
authors.affiliation: Department of Genomics, Life & Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.|Center for Rare Diseases Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Department of Biophysics, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: J B
authors.initials: JB
authors.lastname: Pesquero
authors.affiliation: Department of Genomics, Life & Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.|Center for Rare Diseases Bonn, University Hospital of Bonn, Bonn, Germany.|Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Cichon
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000235:genetics*; D001938:Brazil; D003062:Codon; D005174:Factor XII / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D003062:Codon; D005174:Factor XII
keywords: factor XII; hereditary angio-oedema; homozygosity