title: Genotype-to-phenotype analysis: search for clinical characteristics of a missense change in the GABAA-beta 1 receptor gene.
abstract: Genotype-to-phenotype analysis reverses the classical approach to genetic disease in which an unknown genotype is sought for a known phenotype. This paper provides an example of genotype-to-phenotype analysis for the possible psychiatric effects of a missense mutation (H396Q) at a highly conserved residue of the beta 1 subunit gene of the gamma aminobutyric acid type A receptor. DNA samples from 1,507 Caucasians of Western European descent were screened, and 10 heterozygotes for H396Q were identified. These individuals were matched to homozygous normal individuals by age, gender, and length of available medical records. The complete medical records of these 20 individuals were reviewed blindly by two psychiatrists (D.C.S., L.L.H.) to assess psychiatric symptomatology, with an emphasis on anxiety and related disorders. However, no association was found between this missense change at a conserved amino acid and a dominant neuropsychiatric disease phenotype. Thus, this missense change may be neutral or only mildly deleterious, may only cause recessive disease in rare individuals, or may interact epistatically with some other gene(s).
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Sobell
authors.forename: D C
authors.initials: DC
authors.lastname: Sigurdson
authors.forename: L L
authors.initials: LL
authors.lastname: Heston
authors.forename: W F
authors.initials: WF
authors.lastname: Byerley
authors.forename: S S
authors.initials: SS
authors.lastname: Sommer
mesh_terms: D000368:Aged; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D001523:Mental Disorders / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011963:Receptors, GABA-A / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D011963:Receptors, GABA-A