SINGLE-STRAND CONFORMATIONAL POLYMORPHISM AND DIRECT SEQUENCING APPLIED TO CARRIER TESTING IN FAMILIES WITH ORNITHINE TRANSCARBAMYLASE DEFICIENCY

Single-strand conformational polymorphism (SSCP) and direct sequencing were used to confirm or deny carrier status in three families with or nithine transcarbamylase (OTC) enzyme deficiency. Two male probands wi th ''late onset'' OTC deficiency, whose ''private'' mutations were pre viously characterized, inherited the mutations form their heterozygous mothers. One of the heterozygous mothers had a false negative allopur inol test. Three female siblings of the two male probands were tested, one proved to be a carrier of the respective mutation while the other two were found to have normal alleles. In the third family, the proba nd was a female with ''late onset'' presentation of OTC deficiency. We found a new point mutation in this girl consisting of a guanine-to-cy tosine transversion at nucleotide 520 resulting in a substitution of p roline for alanine at amino acid 142 of the mature OTC protein. We con firmed that this mutation occurred spontaneously and that neither of t he two parents carries this mutation. We conclude that SSCP, in conjun ction with direct sequencing, is a useful technique that can be practi cally applied for carrier testing in families with OTC deficiency.