New mutation versus exclusion at the alpha-1-antitrypsin locus: a multifaceted approach in a problematical paternity case

In a case of disputed paternity with overwhelming indications of fatherhood for the putative father, as supported by serological tests and biostatistical evaluation, a classical exclusion constellation was found at the alpha 1-antitrypsin (PI) locus: mother PI M1; child PI M1M3, and putative father PI M1M2. Additional studies included PI oligonucleotide phenotyping and DNA fingerprint analysis. Results from the entire data set led us to assume a rare genetic event at the paternal PI locus. Intracistronal crossing-over offered the most parsimonious explanation, and was compatible with the PI gene DNA sequence and the amino acid sequences of the molecule and its allelic forms, as well as with the experimental findings.