GENOTYPE-TO-PHENOTYPE ANALYSIS - SEARCH FOR CLINICAL CHARACTERISTICS OF A MISSENSE CHANGE IN THE GABA(A)-BETA-1 RECEPTOR GENE

Genotype-to-phenotype analysis reverses the classical approach to gene tic disease in which an unknown genotype is sought for a known phenoty pe. This paper provides an example of genotype-to-phenotype analysis f or the possible psychiatric effects of a missense mutation (H396Q) at a highly conserved residue of the beta 1 subunit gene of the gamma ami nobutyric acid type A receptor, DNA samples from 1,507 Caucasians of W estern European descent were screened, and 10 heterozygotes for H396Q were identified, These individuals were matched to homozygous normal i ndividuals by age, gender, and length of available medical records, Th e complete medical records of these 20 individuals were reviewed blind ly by two psychiatrists (D.C.S., L.L.H.) to assess psychiatric symptom atology, with an emphasis on anxiety and related disorders, However, n o association was found between this missense change at a conserved am ino acid and a dominant neuropsychiatric disease phenotype, Thus, this missense change may be neutral or only mildly deleterious, may only c ause recessive disease in rare individuals, or may interact epistatica lly with some other gene(s). (C) 1996 Wiley-Liss, Inc.