DNA-based prenatal diagnosis of harlequin ichthyosis and characterization of ABCA12 mutation consequences.

[harlequin ichthyosis]

Until the identification of ABCA 12 as the causative gene , prenatal diagnosis (PD ) for harlequin ichthyosis (HI ) had been performed by electron microscopic observation of fetal skin biopsy samples . We report the first case of HI DNA-based PD . Direct sequence analysis of ABCA 12 revealed that the deceased proband was a compound heterozygote for two novel mutations . The maternal nonsense mutation p .Ser 1249 Term likely leads to nonsense-mediated messenger RNA decay . The paternal mutation c .7436 G >A affects the last codon of exon 50 and was expected to be a splice site mutation . For their third pregnancy , the parents requested PD . Direct sequence analysis of fetal genomic DNA from amniotic fluid cells at 17 weeks gestation revealed the fetus was a compound heterozygote for both mutations . The parents requested the pregnancy to be terminated . Analysis of ABCA 12 transcripts of cultured keratinocytes from the abortus showed the presence of six abnormally spliced products from the allele carrying the splice site mutation . Four of them lead to premature termination codons whereas the two others produced shortened proteins missing 21 and 31 amino acids from the second ATP-binding cassette . This report provides evidence for residual ABCA 12 expression in HI , and demonstrates the efficiency of early DNA-based PD of HI .