Bullous ichthyosiform erythroderma, developmental delay, aortic and pulmonary stenosis in association with a FRA12A

We present an 11-year-old female with bullous ichthyosiform erythroderma (B IE), learning disability, patent ductus arteriosus and mild stenosis of the aortic and pulmonary arteries. Chromosome analysis showed the expression o f the rare folate-sensitive fragile site FRA12A at 12q13 in 8/20 (40%) of b lood lymphocytes cultured in folate-deficient medium in the presence of tri methoprim. Her mother and maternal grandmother are phenotypically normal, b ut her mother shows expression of the same fragile site in 4/20 (20%) of ce lls cultured under the same conditions. Lymphocytes from the grandmother on ly showed expression of the fragile site when cultured in the presence of m ethotrexate in folate deficient medium. Interestingly, two genes (keratin 1 and keratin 2e) which are known to cause BIE map to 12q13. Molecular data is presented excluding three candidate (CCG)(n) repeats within keratin 1 ge ne. We present a review of previously reported FRA12A cases and discuss pos sible molecular explanations for the clinical findings in this patient. Cli n Dysmorphol 9: 213-219 (C) 2000 Lippincott Williams & Wilkins.