Congenital absence of the uterus and vagina (CAUV) is a well known syndrome in which a phenotypic females lack mullerian derived structures. Identification of the genes responsible for this disorder has been hampered because in general patients with CAUV cannot reproduce, and inheritance patterns of mutations cannot be traced. De novo translocation break points have been used successfully to aid in identifying genes responsible for a wide variety disorders and does not rely on a reproductive history for identifying the genes.

Chromosomal studies utilizing high-resolution banding were performed on peripheral leukocytes and fibroblast cultures from various sites on a patient with CAUV.

We have identified tissue specific mosaicism in a patient with CAUV and de novo balanced translocations from leukocyte and tissue fibroblast cultures by GTG banding techniques. Chromosome analysis from leukocyte on the patient’s parents showed normal karyotypes while the patient herself had a more complex pattern. Studies on leukocyte cultures from this patient identified a 46, XX, t(8;13) q22.1;q32.1) de novo balanced reciprocal translocation. Analysis of metaphase spreads from fibroblasts cultures of the buttock region revealed a second set of chromosome mosaicism. One cell line was similar to the leukocyte culture with a 46, XX, t(8:13)(q22.1;q32.1) karyotype. The other cell line had three balanced translocations showing a 46, XX, t(1;12)(q23;q24.3), t(6;6)(q15;p25), t(8;13)(q22;q32) karyotype. These two cell lines were in a ratio of 20: 5 respectively. Chromosome analysis of fibroblast cultures from the breast region shows cells with both the simple and more complex translocation.

These results indicate the importance of analyzing multiple tissue samples in the process of locating de novo break points for gene identification. It also suggests that somatic mosaicism may be a mechanism in the pathogenesis of uterovaginal agenisis. Identification of the genes at the specific break points of these translocations is in progress.