Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is clinically characterized by the presence of two of the three major clinical symptoms: Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Because of its autosomal recessive inheritance, this rare disorder constitutes an interesting model for understanding the molecular background of autoimmunity. Recently, mutations in the autoimmune regulator (AIRE-1) gene have been identified in APECED patients. Here we report, in a large French APECED family, the identification of a novel AIRE-1 missense mutation (Pro326Leu) in association with the Arg257Stop mutation which is detected in more than 80% of mutant Finnish AIRE-1 alleles. This Pro326Leu substitution occurs in the first plant homeodomain (PHD)-type zinc-finger domain of the protein which has been identified in a number of nuclear proteins involved in chromatin-mediated transcriptional regulation, such as ATRX, TIF1, KRIP-1 and Mi-2 autoantigen. This mutation highlights the key role of this amino acid in the structure of the PHD domain and confirms that exon 8 constitutes a mutational hotspot.
Saugier-Veber
P
P
Laboratory of Molecular Genetics, INSERM EMI 9906, University of Rouen, Rouen, France. Pascale.Saugier-Verber@chu-rouen.fr
Drouot
N
N
Wolf
L M
LM
Kuhn
J M
JM
Frébourg
T
T
Lefebvre
H
H
D000328:Adult; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D005602:France; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
D004247:DNA; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000096927:AIRE Protein