ClinVar

Edwards et al. (1990) demonstrated somatic mosaicism for this mutation in the father of 2 children with lethal osteogenesis imperfecta (OI2; 166210), each from a different partner. The mutation was found in 33% of sperm, 67% of lymphocytes, and 100% of dermal fibroblasts. The authors hypothesized that the mutation occurred very early in development in a cell that gave rise to both ectodermal and mesodermal cell lineages. Edwards et al. (1992) stated that despite the high level of mosaicism detected in somatic tissues, the only phenotypic manifestation of OI in the proband (the father) was that he was shorter than his unaffected male relatives and had mild dentinogenesis imperfecta. Thermal stability of type I collagen molecules containing the substitution was decreased but to a lesser extent than that for a nonlethal gly259-to-cys (G259C) substitution of the alpha-2(I) (120160.0017) chain, indicating that this measure of molecular stability may be of limited use in explaining the pathogenesis of OI. Edwards et al. (1992) stated that this was the second family in which recurrence of lethal OI had resulted from parental germline mosaicism for a dominant lethal mutation and the fourth family in which there was molecular evidence of parental mosaicism for a mutation that produced lethal OI. The mosaic parent in all 4 families was also mosaic for the mutation in somatic tissues. Since the mutation was detected in blood from all 4 mosaic individuals but not in DNA from cultured fibroblasts in one, blood may be the best parental somatic tissue to examine for mutation found in a sporadic affected infant.