title: Haploinsufficiency of the SERPINA6 gene is associated with severe muscle fatigue: A de novo mutation in corticosteroid-binding globulin deficiency.
abstract: Corticosteroid-binding globulin (SERPINA6) deficiency is an extremely rare hereditary disorder characterized by reduced corticosteroid-binding capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels associated with hypo-/hypertension and muscle fatigue. Here, we present a patient with severe muscle fatigue, normal blood pressure, and abnormal high saliva cortisol levels following a standardized stress test. This patient was found heterozygous for a de novo 367 asparagine-encoding variant of the corticosteroid-binding globulin gene, previously described as "transcortin Lyon". Both parents were homozygous for the ("wildtype") 367 aspartate-encoding allele. To the best of our knowledge, this case represents the first de novo mutation reported for corticosteroid-binding globulin deficiency, implicating a pathogenic role of variants of SERPINA6 in some cases of muscle fatigue.
authors.affiliation: Department of Clinical and Theoretical Psychobiology, University of Trier, Trier, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Buss
authors.forename: U
authors.initials: U
authors.lastname: Schuelter
authors.forename: J
authors.initials: J
authors.lastname: Hesse
authors.forename: D
authors.initials: D
authors.lastname: Moser
authors.forename: D I
authors.initials: DI
authors.lastname: Phillips
authors.forename: D
authors.initials: D
authors.lastname: Hellhammer
authors.forename: J
authors.initials: J
authors.lastname: Meyer
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D004252:DNA Mutational Analysis; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D018763:Muscle Fatigue / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D012463:Saliva / Q000378:metabolism; D015843:Serpins / Q000172:deficiency* / Q000235:genetics*; D014156:Transcortin
chemical_list: D005819:Genetic Markers; C534935:SERPINA6 protein, human; D015843:Serpins; D014156:Transcortin; D006854:Hydrocortisone