Heterozygosity for the "DN allele" (G533-greater than A) of the beta-hexosaminidase alpha subunit gene identified by direct DNA sequencing in a family with the B1 variant of GM2-gangliosidosis.

Department of Pediatrics, University of Minnesota Medical School, Minneapolis 55455.

A new patient having clinical, pathologic and biochemical features of the exceedingly rate B1 variant of GM2-gangliosidosis is described. This patient, of northern European (non-Ashkenazi) ancestry, is the first affected child of this ethnic background available for molecular genetic analysis; thus, she represented an opportunity to identify a new mutation associated with this phenotype or, conversely, to further characterize the DN allele of the hexosaminidase alpha gene (G533-greater than A) as a more widely distributed mutation not previously observed in this gene pool. As a means of rapid analysis, we report a strategy for PCR amplification and direct DNA sequencing of exon 5 of the hexosaminidase alpha gene, the most frequent site of mutations in this condition. With this technique, the father of the affected child was determined to be heterozygous for the DN allele, while the mother was found to have only the normal sequence in this region. This observation further extends the known geographic and ethnic distribution of this mutation, and suggests the likelihood that the DN allele has been derived by multiple independent mutational events.

PMID: 1318511 [PubMed - indexed for MEDLINE]