Identification of a Familial Mutation Associated with GABA-Transaminase Deficiency Disease

• Published in: Neurobiology of disease Vol. 5; no. 2; pp. 89 - 96
• Main Authors: Medina-Kauwe, Lali K., Nyhan, W.L., Gibson, K.M., Tobin, A.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.1998; Elsevier
• Subjects: 4-Aminobutyrate Transaminase - deficiency; 4-Aminobutyrate Transaminase - genetics; 4-Aminobutyrate Transaminase - metabolism; Amino Acid Metabolism, Inborn Errors - enzymology; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Sequence; Amino Acid Substitution - genetics; Animals; Arginine - genetics; Enzyme Activation - genetics; Humans; Lysine - genetics; Molecular Sequence Data; Mutation, Missense; Pedigree; Rats; Sequence Homology, Amino Acid
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1006/nbdi.1998.0184

GABA-transaminase (GABA-T) deficiency disease is a rare recessive disorder characterized by abnormal development, seizures, and high levels of GABA in serum and cerebrospinal fluid. Although some patients are the offspring of consanguineous marriages, most are not. To identify the molecular basis of this disease, we have determined the sequence of human GABA-T cDNA. We have compared the GABA-T cDNA sequences in cultured cells derived from six healthy controls with those from a GABA-T-deficient patient and both parents. Our data indicate that GABA-T deficiency disease may result from an allele that encodes an R220K substitution.