Cohen-Solal L, Bonaventure J, Maroteaux P
Laboratoire de Physiopathologie, URA 584 CNRS, Hôpital Necker, Paris, France.
Hum Genet. 1991 Jul;87(3):297-301. doi: 10.1007/BF00200907.
Four families presenting with familial osteogenesis imperfecta (OI) have been studied: 2 with the lethal type II and 2 with the severe type III form. Fibroblasts of the patients, all issue from non-consanguineous parents, produced normal and abnormal alpha(I) chains. These heterozygous mutations differentiate the recurrent forms from homozygous mutations characteristic of autosomal recessive forms. Although the identity of the mutations could not be determined, such recurrence of autosomal dominant OI is probably the result of germinal mosaicism in one of the parents. Biochemical results were consistent with a somatic mosaicism in the father's fibroblasts in one family. Moreover, our studies show that not only OI type II but also severe OI type III can arise from gonadal mosaicism. We discuss the importance of such a phenomenon for genetic counseling.
对四个患有家族性成骨不全（OI）的家庭进行了研究：两个家庭患致死性II型，两个家庭患严重III型。患者的成纤维细胞均来自非近亲父母，产生正常和异常的α（I）链。这些杂合突变将复发型与常染色体隐性遗传型的纯合突变区分开来。尽管无法确定突变的身份，但常染色体显性OI的这种复发可能是由于父母一方的生殖系嵌合现象导致的。在一个家庭中，生化结果与父亲成纤维细胞中的体细胞嵌合现象一致。此外，我们的研究表明，不仅II型OI，严重的III型OI也可能由性腺嵌合现象引起。我们讨论了这种现象对遗传咨询的重要性。
