A RADIOGRAPHIC, MORPHOLOGIC, BIOCHEMICAL AND MOLECULAR ANALYSIS OF A CASE OF ACHONDROGENESIS TYPE-II RESULTING FROM SUBSTITUTION FOR A GLYCINE RESIDUE (GLY(691)-]ARG) IN THE TYPE-II COLLAGEN TRIMER

被引:24
作者
MORTIER, GR
WILKIN, DJ
WILCOX, WR
RIMOIN, DL
LACHMAN, RS
EYRE, DR
COHN, DH
机构
[1] CEDARS SINAI MED CTR,STEVEN SPIELBERG PEDIAT RES CTR,AHMANSON PEDIAT CTR,LOS ANGELES,CA 90048
[2] UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024
[3] UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024
[4] UNIV WASHINGTON,ORTHOPAED RES LABS,SEATTLE,WA 98195
关键词
D O I
10.1093/hmg/4.2.285
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The type II colIagenopathies form a continuous spectrum of clinical severity, ranging from lethal achondrogenesis type II and hypochondrogenesis, through spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia and Kniest dysplasia to the Stickier syndrome and familial precocious osteoarthropathy at the mildest end of the spectrum. We have carried out a radiographic, morphologic, biochemical and molecular study in a case of achondrogenesis type II. Electron micrographs showed inclusion bodies of dilated rough endoplasmic reticulum in the chondrocytes and the presence of sparse collagen fibers in the cartilage matrix. Protein analysis of collagen from cartilage indicated posttranslational overmodification of the major cyanogen bromide peptides, and suggested a mutation near the carboxyl terminus of the type II collagen molecule. Analysis at the DNA level demonstrated that the phenotype was produced by a single base change (G-->C) that resulted in the substitution of glycine(691) by arginine in the type II collagen triple helical domain. We confirm previous observations in three cases of hypochondrogenesis that glycine substitutions in the alpha 1(II) chain can result in a phenotype at the most severe end of the type II collagenopathy spectrum.
引用
收藏
页码:285 / 288
页数:4
相关论文
共 22 条
[1]  
BOGAERT R, 1992, J BIOL CHEM, V267, P22522
[2]   ACHONDROGENESIS-II HYPOCHONDROGENESIS - VARIABILITY VERSUS HETEROGENEITY [J].
BOROCHOWITZ, Z ;
ORNOY, A ;
LACHMAN, R ;
RIMOIN, DL .
AMERICAN JOURNAL OF MEDICAL GENETICS, 1986, 24 (02) :273-288
[3]  
CHAN D, 1991, J BIOL CHEM, V266, P12487
[4]   ACHONDROGENESIS - A REVIEW WITH SPECIAL CONSIDERATION OF ACHONDROGENESIS TYPE-II (LANGER-SALDINO) [J].
CHEN, H ;
LIU, CT ;
YANG, SS .
AMERICAN JOURNAL OF MEDICAL GENETICS, 1981, 10 (04) :379-394
[5]   THE CLINICAL-FEATURES OF SPONDYLOEPIPHYSEAL DYSPLASIA CONGENITA RESULTING FROM THE SUBSTITUTION OF GLYCINE-997 BY SERINE IN THE ALPHA-1(II) CHAIN OF TYPE-II COLLAGEN [J].
COLE, WG ;
HALL, RK ;
ROGERS, JG .
JOURNAL OF MEDICAL GENETICS, 1993, 30 (01) :27-35
[6]  
EYRE DR, 1986, AM J HUM GENET, V39, P52
[7]   TYPE-II COLLAGEN DEFICIENCY IN ACHONDROGENESIS (LANGER-SALDINO) [J].
EYRE, DR .
PATHOLOGY AND IMMUNOPATHOLOGY RESEARCH, 1988, 7 (1-2) :90-94
[8]  
GODFREY M, 1988, AM J HUM GENET, V43, P894
[9]   APPLICATION OF STAINS-ALL FOR DEMARCATION OF CEMENT LINES IN METHACRYLATE EMBEDDED BONE [J].
GRUBER, HE ;
MEKIKIAN, P .
BIOTECHNIC & HISTOCHEMISTRY, 1991, 66 (04) :181-184
[10]  
GRUBER HE, 1990, J ANAT, V173, P69