Genotyping and prenatal assessment of collagen lysyl hydroxylase deficiency in a family with Ehlers-Danlos syndrome type VI.
Collagen lysyl and prolyl hydroxylase activities were measured in cultured fibroblasts from a child with clinical features of Ehlers-Danlos syndrome. Lysyl-to-prolyl hydroxylase activity ratios in cells from the proband, mother, father, and control were .24, .86, .52, and 1.00, respectively, providing a biochemical diagnosis of Ehlers-Danlos syndrome type VI and indicating an autosomal recessive mode of inheritance in this family. Prenatal assessment of lysyl hydroxylase deficiency was requested and accomplished for the first time during a subsequent pregnancy in the family. A series of control cultures established lysyl hydroxylase activity to be similar in cultured amniotic fluid cells (AF and F cells) and in cultured dermal fibroblasts. Cultured F and AF cells from the monitored pregnancy had enzyme activity similar to controls, indicating that the fetus should not be affected by lysyl hydroxylase deficiency. This finding was confirmed by demonstration of normal lysyl hydroxylase activity in fibroblasts cultured from the newborn baby. These studies show that cells cultured from second trimester amniotic fluid have collagen lysyl hydroxylase activity similar to that in dermal fibroblasts, making prenatal diagnosis of lysyl hydroxylase deficiency possible.
D000328:Adult; D000653:Amniotic Fluid / Q000201:enzymology; D002478:Cells, Cultured; D002648:Child; D004796:Clinical Enzyme Tests; D003094:Collagen / Q000378:metabolism*; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000172:deficiency* / Q000235:genetics; D011393:Procollagen-Proline Dioxygenase / Q000172:deficiency / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000201:enzymology*
D003094:Collagen; D006899:Mixed Function Oxygenases; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase