COLLAGEN TYPE-VI GENE-EXPRESSION IN THE SKIN OF TRISOMY-21 FETUSES

Objective: To determine whether the mechanism for the retention of int erstitial fluid in trisomy 21 fetuses presenting with nuchal transluce ncy at 10-14 weeks' gestation is an alteration in the composition of c ollagen type VI, which is normally a triple helix formed of three sing le chains, alpha 1, alpha 2, and alpha 3. The genes responsible for th e alpha 1 and alpha 2 chains, COL6A1 and COL6A2, are located on chromo some 21 and therefore may be overexpressed in trisomy 21, whereas COL6 A3 is located in chromosome 2. Methods: Skin tissue was obtained after termination of pregnancy at 11-16 weeks' gestation in five fetuses wi th trisomy 21 and five normal controls. Total RNA was extracted and th e steady-state levels of COL6A1 and COL6A3 mRNA expression of the gene transcripts were determined. Additionally, the distribution of collag en type VI in the skin of trisomy 21 and normal fetuses was analyzed u sing an immunohistochemical method. Results: The ratio of the normaliz ed densitometric scores for the mRNA expression of COL6A1 to COL6A3 in the skin of trisomy 21 fetuses was twice as high as in normal fetuses . Immunohistochemistry demonstrated that in trisomy 21 fetuses collage n type VI formed a dense network extending from the epidermal basement membrane to the subcutis, whereas in normal fetuses dense staining wa s confined to the upper region of the dermis. Conclusion: The distribu tion for collagen type VI is different from normal in the skin of tris omy 21 fetuses, and there is overexpression of COL6A1 compared with CO L6A3. (C) 1998 by The American College of Obstetricians and Gynecologi sts.