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Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease.
Hum Mutat. 1992; 1(1):47-54.HM

Abstract

We have determined that a man, ascertained because he fathered a child with lethal osteogenesis imperfecta (OI) with each of two partners, is mosaic in both his germline and somatic tissues for a mutation in the COL1A2 gene which encodes the pro alpha 2(I) chain of type I procollagen. His dermal fibroblasts were previously shown to synthesize a population of cysteine-containing alpha 2(I) chains that were posttranslationally overmodified. DNA sequence analysis of COL1A2 cDNAs demonstrated that the cysteine-containing chain resulted from a point mutation (G to T) in the first position of the codon for the glycine at residue 472 of the triple helical domain. Genomic DNA from the one available affected infant contained the mutant and normal COL1A2 alleles in equal proportion. Examination of DNA from several tissues of the father showed that the mutant allele was present in approximately 40% of his sperm, 80% of his lymphocytes, and nearly 100% of his dermal fibroblasts. Despite the high level of mosaicism detected in somatic tissues, the only phenotypic manifestation of OI in the proband 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 for a nonlethal cysteine for glycine substitution at residue 259 of alpha 2(I), indicating that this measure of molecular stability may be of limited use in explaining the pathogenesis of osteogenesis imperfecta.

Authors+Show Affiliations

Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center, Cedars Sinai Medical Center, Los Angeles, California 90048.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1301191

Citation

Edwards, M J., et al. "Recurrence of Lethal Osteogenesis Imperfecta Due to Parental Mosaicism for a Mutation in the COL1A2 Gene of Type I Collagen. the Mosaic Parent Exhibits Phenotypic Features of a Mild Form of the Disease." Human Mutation, vol. 1, no. 1, 1992, pp. 47-54.
Edwards MJ, Wenstrup RJ, Byers PH, et al. Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease. Hum Mutat. 1992;1(1):47-54.
Edwards, M. J., Wenstrup, R. J., Byers, P. H., & Cohn, D. H. (1992). Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease. Human Mutation, 1(1), 47-54.
Edwards MJ, et al. Recurrence of Lethal Osteogenesis Imperfecta Due to Parental Mosaicism for a Mutation in the COL1A2 Gene of Type I Collagen. the Mosaic Parent Exhibits Phenotypic Features of a Mild Form of the Disease. Hum Mutat. 1992;1(1):47-54. PubMed PMID: 1301191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease. AU - Edwards,M J, AU - Wenstrup,R J, AU - Byers,P H, AU - Cohn,D H, PY - 1992/1/1/pubmed PY - 1992/1/1/medline PY - 1992/1/1/entrez SP - 47 EP - 54 JF - Human mutation JO - Hum Mutat VL - 1 IS - 1 N2 - We have determined that a man, ascertained because he fathered a child with lethal osteogenesis imperfecta (OI) with each of two partners, is mosaic in both his germline and somatic tissues for a mutation in the COL1A2 gene which encodes the pro alpha 2(I) chain of type I procollagen. His dermal fibroblasts were previously shown to synthesize a population of cysteine-containing alpha 2(I) chains that were posttranslationally overmodified. DNA sequence analysis of COL1A2 cDNAs demonstrated that the cysteine-containing chain resulted from a point mutation (G to T) in the first position of the codon for the glycine at residue 472 of the triple helical domain. Genomic DNA from the one available affected infant contained the mutant and normal COL1A2 alleles in equal proportion. Examination of DNA from several tissues of the father showed that the mutant allele was present in approximately 40% of his sperm, 80% of his lymphocytes, and nearly 100% of his dermal fibroblasts. Despite the high level of mosaicism detected in somatic tissues, the only phenotypic manifestation of OI in the proband 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 for a nonlethal cysteine for glycine substitution at residue 259 of alpha 2(I), indicating that this measure of molecular stability may be of limited use in explaining the pathogenesis of osteogenesis imperfecta. SN - 1059-7794 UR - https://www.unboundmedicine.com/medline/citation/1301191/Recurrence_of_lethal_osteogenesis_imperfecta_due_to_parental_mosaicism_for_a_mutation_in_the_COL1A2_gene_of_type_I_collagen__The_mosaic_parent_exhibits_phenotypic_features_of_a_mild_form_of_the_disease_ L2 - https://doi.org/10.1002/humu.1380010108 DB - PRIME DP - Unbound Medicine ER -