A novel arylsulfatase A protein variant and genotype in two patients with major depression

• Published in: Journal of affective disorders Vol. 40; no. 3; pp. 137 - 147
• Main Authors: Ricketts, Michael H., Amsterdam, Jay D., Park, David S., Yang, Rong-Sheng, Poretz, Ronald D., Zhang, Xiaoping, Fanale, Michelle, Baddoo, Andrew, Manowitz, Paul
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 14-10-1996; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Arylsulfatase A; Biological and medical sciences; Blood Protein Electrophoresis; Cerebroside-Sulfatase - deficiency; Cerebroside-Sulfatase - genetics; Depression; Depressive Disorder - diagnosis; Depressive Disorder - enzymology; Depressive Disorder - genetics; DNA Mutational Analysis; Female; Gene mutation; Genetic Variation; Humans; Isoenzymes - genetics; Leukodystrophy, Metachromatic - diagnosis; Leukodystrophy, Metachromatic - enzymology; Leukodystrophy, Metachromatic - genetics; Male; Medical sciences; Metachromatic leukodystrophy; Middle Aged; Mood disorders; Pedigree; Pseudodeficiency; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Metachromatic leukodystrophy; Arylsulfatase A; Depression; Pseudodeficiency; Gene mutation; Human; Mood disorder; Cerebroside-sulfatase; Genetic inheritance; Enzyme; Hydrolases; Esterases; Mutation; Sulfuric ester hydrolases
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/0165-0327(96)00051-1

A new, ‘diffuse, multiple banding’, electrophoretic variant of arylsulfatase A protein was found in two patients with major depression. Protein analyses showed that this variant and the normal enzyme differed in amino acid sequence and/or post-translational modifications unrelated to phosphate groups and oligomannose glycans. Analysis of the arylsulfatase A genes from a subject with the new variant identified three mutations; one gene had the two mutations associated with arylsulfatase A pseudodeficiency, and the other had a G to T transversion which changes a tryptophan to cysteine in the protein. These mutations result in an arylsulfatase A protein heteromer with diffuse electrophoretic banding. The possible association of these mutations with major depression is discussed.