Segregation analysis ofdominant osteogenesis imperfecta inItaly

Wehaveperformed linkage analysis insevenItalian families, inwhichmildosteogenesis imperfecta (OI) segregated asadominant trait, bymeansofsix DNA restriction fragment length polymorphisms (RFLPs) oftypeIcoliagen genes. 01typeIwas linked totheal(I) gene(COLlAl) intwofamilies, andtothea2(I) gene(COL1A2) inonefamily. OI typeIVsegregated withCOL1A2intwofamilies. In twoOItypeIfamilies, themolecular genetic data wereinsufficient forexclusion ofonegene.Four DNA polymorphisms wereparticularly informative forcosegregation analysis of01inItalian kindreds. Newdataatthebiochemical, genetic, andmolecular levels haveindicated inrecent years theassociation of osteogenesis imperfecta (OI)withvarious mutations inthegenes (COLlAlandCOLIA2)whichencode fortypeIprocollagen. 12Thestriking clinical heterogeneity3 ofbrittle bonedisease isemphasised bythe molecular datawhichhavebeenaccumulating inthe last three years; eachmutation studied sofarisa different one.Theyoccur sporadically intheseverest cases, whiletheyaretransmitted inanautosomal dominant fashion inmilder cases. Mutations which cause structural abnormalities ofproal(I) andproa2(I) chains aremorecommonly found insevere variants of 01 andcanoften beshownbythebiochemical analysis ofcollagen I.4 Inmilder OIvariants (01typeIandtypeIV according toSillence eta13), whichcanbedominantly inherited, analysis andidentification ofthemutations arefarless accessible since theyoften donotproduce