ClinVar

In a family in which the mother and 4 children were affected with autosomal dominant osteogenesis imperfecta type IV (166220), Lund et al. (1996) identified an in-frame deletion of nucleotides 1964-1966 (GGC) from a series of 6 nucleotides (GAG/GCT) encoding codons 437 and 438 in exon 27 of the COL1A1 gene, resulting in the removal of an alanine residue at position 438 and a glu437-to-asp (E437D) substitution in the alpha-1 (I) collagen chain. The father was clinically normal and lacked the mutation, which was detected by restriction enzyme analysis in all affected family members. Clinical variation among affected members was considerable; the most consistent clinical features were reduced height and extraosseous manifestations of OI. The mother was 136 cm tall and her 19-year-old daughter 132 cm tall. A 28-year-old son was 137 cm tall but a 24-year-old son was 162 cm tall and a 31-year-old daughter 151 cm tall. All had white sclerae and dentinogenesis imperfecta. The heights of the mother, 2 daughters (31 and 19 years of age), and 2 sons (28 and 24 years of age), were 136, 151, 132, 137, and 162 cm, respectively. The mother and eldest sib had otosclerosis. The 24-year-old son was physically active and capable in sports, including contact sports, and his OI diagnosis was questioned by other members of the family.