Identification of two novel mutations in the hydroxymethylbilane synthase gene in three patients from two unrelated families with acute intermittent porphyria.

We have screened the hydroxymethylbilane synthase cDNAs of 3 patients from 2 families suffering from acute intermittent porphyria (AIP) from Scotland and South Africa using heteroduplex and chemical cleavage of mismatch analyses. Direct sequencing was used to characterise the mutations. The two novel mutations identified were a missense mutation at nucleotide position 64 in exon 3 (R22C) and a single base-pair deletion in exon 15. These mutations are predicted to affect the normal function of the enzyme and, therefore, are expected to be the primary cause of disease in these patients.

Trisomy 1 mosaicism only detected on a direct chromosome preparation in a neonate.

A patient is described with trisomy 1 mosaicism which was discovered on 24-h culture of a neonatal blood sample, but was not detectable on subsequent 48- and 72-h cultures. This result complements other recent reports and has important implications for the detection of mosaicism in neonates.