TRANSLOCATION BREAKPOINTS IN 3 PATIENTS WITH CAMPOMELIC DYSPLASIA ANDAUTOSOMAL SEX REVERSAL MAP MORE THAN 130 KB FROM SOX9

Campomelic dysplasia (CMPD1) and autosomal XY sex reversal (SRA1) are caused by mutations in the SRY-related gene SOX9 on 17q. Unexpectedly, the 17q breakpoints in four CMPD1 translocation cases previously anal yzed by us and others map 50 kb or more from SOX9. Here, we present cl inical, cytogenetic, and molecular data from a new CMPD1/SRA1 patient with t(6; 17) (q14; q24). Fluorescence in situ hybridization has shown that the 17q breakpoint in this case maps to the same region as the b reakpoints in the other translocation cases, at least 130 kb from SOX9 . Likewise, the breakpoints in two of the previously described cases a lso map more than 130 kb and, as shown by pulsed field gel electrophor esis analysis, at most 400 kb or 690 kb from SOX9. By using a SOX9 cod ing sequence polymorphism, expression of both SOX9 alleles has been de monstrated by the reverse transcriptase polymerase chain reaction in l ymphoblastoid cells from one of the translocation cases.