Nonexpression of cartilage type II collagen in a case of Langer-Saldino achondrogenesis.

A lethal short-limbed dwarfism was diagnosed at autopsy as the Langer-Saldino variant of achondrogenesis by radiological, histological, and gross pathological criteria. Cartilage was obtained for biochemical and ultrastructural analyses from the ends of long bones, from ribs and from a scapula of the newborn infant. At all sites, it had an abnormal gelatinous texture and translucent appearance. Biochemical analyses of the cartilages to identify pepsin-solubilized collagen alpha-chains and collagen-specific CNBr-peptides failed to detect type II collagen at any site where it would normally be the main constituent. Instead, type I was the predominant collagen present. However, three cartilage-specific minor collagen chains identified as 1 alpha, 2 alpha, and 3 alpha chains by their electrophoretic mobility were present at about 10% of the total collagen. Cartilage-specific proteoglycans also appeared to be abundant in the tissue judging by its high hexosamine content and high ratio of galactosamine to glucosamine. The findings indicate that a chondrocyte phenotype had differentiated but without the expression of type II collagen. In addition to the skeletal abnormalities, the severe pulmonary hypoplasia was also felt to be directly related to the underlying pathology in collagen expression. The term chondrogenesis imperfecta rather than achondrogenesis should be considered a more accurate description of this and related conditions.

[1]  D. Barlow,et al.  Chromosomal assignments of the genes coding for human types II, III, and IV collagen: a dispersed gene family. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[2]  M. Sobel,et al.  Analysis of cDNA and genomic clones coding for the proα1 chain of calf Type II collagen , 1985 .

[3]  P. Tsipouras,et al.  Isolation and partial characterization of the entire human pro alpha 1(II) collagen gene. , 1985, Nucleic acids research.

[4]  D. Eyre,et al.  828 ABNORMAL CARTILAGE COLLAGENS IN ACHONDROGENESIS II , 1985, Pediatric Research.

[5]  T. Schmid,et al.  Immunohistochemical localization of short chain cartilage collagen (type X) in avian tissues , 1985, The Journal of cell biology.

[6]  B. Olsen,et al.  The Structure of Type IX Collagen a , 1985, The Journal of biological chemistry.

[7]  P. Byers,et al.  The molecular basis of clinical heterogeneity in osteogenesis imperfecta: Mutations in type I collagen genes have different effects on collagen processing , 1985 .

[8]  B. Olsen,et al.  The structure of type IX collagen. , 1985, Annals of the New York Academy of Sciences.

[9]  V. Sheffield,et al.  Copy number of the chicken type II procollagen gene. , 1985, Collagen and related research.

[10]  K. Kivirikko,et al.  Heritable diseases of collagen. , 1984, The New England journal of medicine.

[11]  W. Horton Histochemistry, a valuable tool in connective tissue research. , 1984, Collagen and related research.

[12]  D. Woolley,et al.  All three chains of 1α2α3α collagen from hyaline cartilage resist human collagenase , 1984 .

[13]  D. Eyre,et al.  Collagen of fibrocartilage: a distinctive molecular phenotype in bovine meniscus , 1983, FEBS letters.

[14]  H. Barrach,et al.  Absence of proteoglycan core protein in cartilage from the cmd/cmd (cartilage matrix deficiency) mouse. , 1981, The Journal of biological chemistry.

[15]  J. Murphy,et al.  The structural basis of persistent pulmonary hypertension of the newborn infant. , 1981, The Journal of pediatrics.

[16]  P. Goetinck,et al.  A comparison of the proteoglycans synthesized in Meckel's and sternal cartilage from normal and nanomelic chick embryos. , 1979, Developmental biology.

[17]  R. Burgeson,et al.  Collagen heterogeneity in human cartilage: identification of several new collagen chains. , 1979, Biochemical and biophysical research communications.

[18]  K. von der Mark,et al.  The influence of proteoglycans on the macromolecular structure of collagen. , 1978, Supplementum ... ad Thrombosis and haemostasis.

[19]  J. Bernstein Pathology of the Fetus and the Infant , 1976 .

[20]  D. Eyre,et al.  The distribution of different molecular species of collagen in fibrous, elastic and hyaline cartilages of the pig. , 1975, Biochemical Journal.

[21]  G. Garewal,et al.  Two types of heritable lethal achondrogenesis. , 1974, The Journal of pediatrics.

[22]  D. Rimoin,et al.  Histologic studies in the chondrodystrophies. , 1974, Birth defects original article series.

[23]  M. Rejent,et al.  Achondrogenesis: case report and review of the literature. , 1973, The Journal of pediatrics.

[24]  R. Saldino Radiographic diagnosis of neonatal short-limbed dwarfism. , 1973, Medical radiography and photography.

[25]  R. Saldino Lethal short-limbed dwarfism: achondrogenesis and thanatophoric dwarfism. , 1971, The American journal of roentgenology, radium therapy, and nuclear medicine.

[26]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[27]  L. Langer,et al.  Thanatophoric dwarfism. A condition confused with achondroplasia in the neonate, with brief comments on achondrogenesis and homozygous achondroplasia. , 1969, Radiology.

[28]  V. McKusick GENERALIZED GENETIC DISORDERS OF THE OSSEOUS SKELETON. , 1965, JAMA.

[29]  A. Quelce-Salgado A NEW TYPE OF DWARFISM WITH VARIOUS BONE APLASIAS AND HYPOPLASIAS OF THE EXTREMITIES. , 1964, Acta genetica et statistica medica.