caa a22 4500 397575645 CHVBK 20180308164855.0 cr unu---uuuuu 161202e199610 xx s 000 0 eng 10.1093/hmg/5.10.1625 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.10.1625 A Novel Germ Line Mutation in SOX9 Causes Familial Campomelic Dysplasia and Sex Reversal [Elektronische Daten] [Fergus J. Cameron, Robyn M. Hageman, Claire Cooke-Yarborough, Cheni Kwok, Linda L. Goodwin, David O. Sillence, Andrew H. Sinclair] Mutations in the gene SOX9 result in the syndrome of campomelic dysplasia (CD) which includes sex-reversal in 75% of 46,XY affected individuals. These mutations only affect a single allele of SOX9 suggesting a dominant mode of inheritance for this syndrome. Consequently, CD and autosomal sex reversal may result from haploinsufficiency of SOX9. The SOX9 gene maps to the long arm of human chromosome 17 and translocations in this region also result in CD. We report a family in which there were three affected patients, two of whom showed 46,XY sex-reversal. Interestingly, despite all three patients being heterozygous for a familial mutation in SOX9 (insertion of a cytosine residue at nucleotide position 1096), their gonadal phenotypes varied widely. The proband was found to have 46,XY true hermaphroditism with ambiguous genitalia. The other two sibs were 46,XY and 46,XX, and both had bilateral ovaries with normal female genitalia. The somatic cells in both parents revealed wild-type SOX9 nucleotide sequences. However, mutational analysis of the SOX9 gene in the father's germ cells revealed they were mosaic for mutant and wild-type sequences. This family is particularly informative as it demonstrates that the same SOX9 mutation can produce very different 46,XY gonadal phenotypes. The range of gonadal morphologies observed may be explained by several possible mechanisms such as variable penetrance of the mutation, increased activity of the non-mutant SOX9 allele or stochastic environmental factors. These results also demonstrate that paternal germ cell mosaicism of a mutant SOX9sequence can result in a CD phenotype amongst his offspring. © 1996 Oxford University Press Cameron Fergus J. Department of Paediatrics and Centre for Hormone Research, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut Hageman Robyn M. Department of Paediatrics and Centre for Hormone Research, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut Cooke-Yarborough Claire Department of Anatomical Pathology, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut Kwok Cheni Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK aut Goodwin Linda L. Department of Clinical Genetics, The New Children's Hospital, Sydney, NSW 2124, Australia aut Sillence David O. Department of Clinical Genetics, The New Children's Hospital, Sydney, NSW 2124, Australia aut Sinclair Andrew H. Department of Paediatrics and Centre for Hormone Research, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut Human Molecular Genetics Oxford University Press 5/10(1996-10), 1625-1630 0964-6906 5:10<1625 1996 5 hmg https://doi.org/10.1093/hmg/5.10.1625 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.10.1625 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cameron Fergus J. Department of Paediatrics and Centre for Hormone Research, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut NATIONALLICENCE 700 1- Hageman Robyn M. Department of Paediatrics and Centre for Hormone Research, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut NATIONALLICENCE 700 1- Cooke-Yarborough Claire Department of Anatomical Pathology, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut NATIONALLICENCE 700 1- Kwok Cheni Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK aut NATIONALLICENCE 700 1- Goodwin Linda L. Department of Clinical Genetics, The New Children's Hospital, Sydney, NSW 2124, Australia aut NATIONALLICENCE 700 1- Sillence David O. Department of Clinical Genetics, The New Children's Hospital, Sydney, NSW 2124, Australia aut NATIONALLICENCE 700 1- Sinclair Andrew H. Department of Paediatrics and Centre for Hormone Research, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/10(1996-10), 1625-1630 0964-6906 5:10<1625 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford