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 characterized by a variety of skeletal anomalies, low-set ears and, in nearly half of genotypical-male patients, sex reversal. Observations of chromosomal translocations involving chromosome 17q24-q25 in several CMPD patients have implied that disruption of one or more genes in the breakpoint region is responsible for this disease. Using fluorescence in situ hybridization, we mapped the chromosome-17 breakpoint in a patient with acampomelic CMPD and sex reversal, who carries a de novo constitutional t(12;17) translocation, between two known cosmid markers in the 17q24-q25 region. Through positional cloning, we isolated a 3.5 kb cDNA that is located at a close but distinct position from the SOX9 gene, from the region surrounding this breakpoint. Its mRNA, approximately 3.7 kb long, was expressed specifically in testis among 16 adult tissues examined by Northern blot analysis. As we were unable to find any long open reading frame in the 3.5 kb cDNA sequence or to detect any peptide following an in vitro translation experiment using RNA transcribed from this cDNA, we speculate that this gene may play a critical role in differentiation or sex determination as a functional RNA.