Re. Brenner et al., PROLIFERATION AND COLLAGEN BIOSYNTHESIS OF OSTEOBLASTS AND CHONDROCYTES IN SHORT RIB SYNDROME TYPE BEEMER, American journal of medical genetics, 46(5), 1993, pp. 584-591
We report on a case of lethal short-limbed skeletal dysplasia with ext
remely short ribs, median cleft upper lip and palate, malrotation of i
ntestine, lung hypoplasia with bilateral segmentation defect, atrial s
eptum defect, union of distal urethra and vagina, and complex brain ma
lformations. Based on radiological criteria and the pattern of associa
ted abnormalities a short rib syndrome without polydactyly (Type Beeme
r) was diagnosed. Morphologically, the growth plate showed a reduced p
roliferation zone and an enlarged zone of hypertrophic cartilage. In a
ddition, islands of persistent hypertrophic cartilage were present eve
n in the metaphysis. In monolayer cell cultures supplemented with 10%
fetal calf serum proliferation was normal in articular chondrocytes, r
educed in costal chondrocytes, and elevated in osteoblasts from the pa
tient. Clonal growth of costal and articular chondrocytes in methylcel
lulose could be stimulated normally by insulin-like growth factor-I (I
GF-I), IGF-II, and human growth hormone (hGH). However, the response t
o transforming growth factor beta1 (TGF-beta1) was markedly elevated i
n articular chondrocytes of the patient compared to those of 3 fetal c
ontrols. Quantitative collagen synthesis in both osteoblasts and chond
rocytes from the patient did not differ significantly from that of con
trols. Osteoblasts synthesized predominantly collagen I and minor amou
nts of collagen III, chondrocytes synthesized primarily collagen II. A
ll collagen chains including CNBr-peptides of collagen II showed norma
l migration in PAA gel electrophoresis.