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 .

Diseases
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Diseases presenting "prenatal diagnosis" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

classical phenylketonuria

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cystinuria

dentinogenesis imperfecta

epidermolysis bullosa simplex

harlequin ichthyosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

kindler syndrome

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neonatal adrenoleukodystrophy

oculocutaneous albinism

omenn syndrome

phenylketonuria

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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