Isolation of a testis-specific cDNA on chromosome 17q from a region adjacent to the breakpoint of t(12;17) observed in a patient with acampomelic campomelic dysplasia and sex reversal

Campomelic dysplasia (CMPD), a rare congenital disorder, is characterizedby a variety of skeletal anomalies, low-set ears and, in nearly half ofgenotypical-male patients, sex reversal. Observations of chromosomaltranslocations involving chromosome 17q24-q25 in several CMPD patients haveimplied that disruption of one or more genes in the breakpoint region isresponsible for this disease. Using fluorescence in situ hybridization, wemapped the chromosome-17 breakpoint in a patient with acampomelic CMPD andsex reversal, who carries a de novo constitutional t(12;17) translocation,between two known cosmid markers in the 17q24-q25 region. Throughpositional cloning, we isolated a 3.5 kb cDNA that is located at a closebut distinct position from the SOX9 gene, from the region surrounding thisbreakpoint. Its mRNA, approximately 3.7 kb long, was expressed specificallyin testis among 16 adult tissues examined by Northern blot analysis. As wewere unable to find any long open reading frame in the 3.5 kb cDNA sequenceor to detect any peptide following an in vitro translation experiment usingRNA transcribed from this cDNA, we speculate that this gene may play acritical role in differentiation or sex determination as a functional RNA.