Recurrence of osteogenesis imperfecta because of paternal mosaicism: Gly862-->Ser substitution in a type I collagen gene (COL1A1).
We determined that two siblings with type III osteogenesis imperfecta (OI) had the same single base substitution that converted the codon for glycine (Gly) 862 to a codon for serine (Ser) in exon 44 of the alpha 1 chain of the type I (alpha 1(I)) collagen gene (COL1A1). The mutation was also detected in various paternal tissues; the mutant allele accounted for approximately 11% of the COL1A1 alleles in blood, 24% of those in fibroblasts, and 43% of those in sperm determined by allele-specific colony hybridization using amplified genomic sequences. These findings demonstrate that germ-line mosaicism in the phenotypically normal father is responsible for the recurrence. There is a cluster of serine substitutions for Gly (Gly832, Gly844 and Gly901) which is associated with nonlethal phenotypes and which is located between two lethal clusters. In the cases studied here, a Gly862-->Ser mutation was identified that is located inside the nonlethal cluster.
Namikawa
C
C
Department of Biochemistry, Nagoya City University Medical School, Japan.
Suzumori
K
K
Fukushima
Y
Y
Sasaki
M
M
Hata
A
A
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D014018:Tissue Distribution
D018076:DNA, Complementary; D003094:Collagen