Moderately severe osteogenesis imperfecta associated with substitutions of serine for glycine in the alpha 1(I) chain of type I collagen.
We have examined the type I collagen protein, RNA, and cDNA of 2 children with moderately severe (type IV) osteogenesis imperfecta (OI). They have in common a non-lethal form of OI with ambulatory potential, overmodification of type I collagen protein, and a substitution of serine for glycine in the collagen chain produced by one alpha 1(I) allele. The first child (Marini et al.: J Biol Chem 264:11893-11900, 1989) is now 7 years old, with the height of a 3-year-old. Her course includes significant remodeling of lower long bones and 4 femur fractures. She walks independently. A mishmatch was detected in her alpha 1(I) mRNA using RNA/RNA hybrids; it was demonstrated to be due to a G-->A point mutation in one allele of alpha 1(I), resulting in the substitution of serine for glycine 832. The second child is now 6 1/2 years old, with the height of 1 1/2-year-old. Her history includes significant bowing of femurs and tibias, 6 femur fractures, S-curve scoliosis, compression of all lumbar vertebrae, and limited short-distance walking with braces. Her alpha 1(I) mRNA has also been studied by RNA hybrid analysis; there is a single G-->A change in one alpha 1(I) allele causing the substitution of serine for gly 352. Both children have moderately severe OI. However, the serine substitution at gly 352 is associated with a more severe phenotype then is the serine substitution at gly 832. Compared to substitutions described in other cases of OI, the serine 352 is located in the middle of a cluster of cysteine substitutions associated with non-lethal OI.(ABSTRACT TRUNCATED AT 250 WORDS)
Marini
J C
JC
Unit on Connective Tissue Disorders, Human Genetics Branch, NICHD, NIH, Bethesda, Maryland 20892.
Lewis
M B
MB
Chen
K
K
D002648:Child; D003094:Collagen / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005998:Glycine / Q000235:genetics*; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D017354:Point Mutation; D011347:Procollagen / Q000235:genetics; D011859:Radiography; D012694:Serine / Q000235:genetics*
D011347:Procollagen; D012694:Serine; D003094:Collagen; D005998:Glycine