Paternal mosaicism for a COL1A1 dominant mutation (α1 Ser-415) causes recurrent osteogenesis imperfecta
Corresponding Author
Monica Mottes
Istituto di Scienze Biologiche, Università di Verona, Italy
Istituto di Scienze Biologiche, Università di Verona, ItalySearch for more papers by this authorM. Gomez Macarena Lira
Istituto di Scienze Biologiche, Università di Verona, Italy
Search for more papers by this authorMaurizia Valli
Dipartimento di Biochimica, Università di Pavia, Italy
Search for more papers by this authorGioacchino Scarano
Centro di Genetica Medica, Ospedale di Avellino, Italy; Fax:3945-809-8180
Search for more papers by this authorFortunato Lonardo
Centro di Genetica Medica, Ospedale di Avellino, Italy; Fax:3945-809-8180
Search for more papers by this authorAntonella Forlino
Dipartimento di Biochimica, Università di Pavia, Italy
Search for more papers by this authorGiuseppe Cetta
Dipartimento di Biochimica, Università di Pavia, Italy
Search for more papers by this authorPier Franco Pignatti
Istituto di Scienze Biologiche, Università di Verona, Italy
Search for more papers by this authorCorresponding Author
Monica Mottes
Istituto di Scienze Biologiche, Università di Verona, Italy
Istituto di Scienze Biologiche, Università di Verona, ItalySearch for more papers by this authorM. Gomez Macarena Lira
Istituto di Scienze Biologiche, Università di Verona, Italy
Search for more papers by this authorMaurizia Valli
Dipartimento di Biochimica, Università di Pavia, Italy
Search for more papers by this authorGioacchino Scarano
Centro di Genetica Medica, Ospedale di Avellino, Italy; Fax:3945-809-8180
Search for more papers by this authorFortunato Lonardo
Centro di Genetica Medica, Ospedale di Avellino, Italy; Fax:3945-809-8180
Search for more papers by this authorAntonella Forlino
Dipartimento di Biochimica, Università di Pavia, Italy
Search for more papers by this authorGiuseppe Cetta
Dipartimento di Biochimica, Università di Pavia, Italy
Search for more papers by this authorPier Franco Pignatti
Istituto di Scienze Biologiche, Università di Verona, Italy
Search for more papers by this authorAbstract
We describe a dominant point mutation in the COL1A1 gene causing extremely severe osteogenesis imperfecta (OI type II/III) which was detected in the dermal fibroblasts of a proband, diagnosed by ultrasonography at 24 weeks of gestation. Type I collagen secretion was reduced and proαl(I) chains were overmodified. The mutation was localised in one COL1A1 allele by chemical cleavage of mismatched bases in normal cDNA/proband's mRNA heteroduplexes, and identified by cloning and sequencing. A G-to-A transition which causes the Substitution of Gly-415 with serine in the a α1(I) triple helical domain was found. The same mutation was detected in the father's spermatozoa and lymphocytes. Mosaicism in the father's germline explains the occurrence in the family of two additional OI pregnancies, which were documented by X-ray and ultrasound investigations. © 1993 Wiley-Liss, Inc.
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