Abstract
Cryptorchidism and hypospadias are the two most common abnormalities of the external genitalia in the male. Recent studies reveal a doubling of the frequency of these abnormalities in the last 20 years. In order to understand environmental influences that may be increasing the incidences, it is helpful to understand the genetic pathways that may be perturbed. Several chromosomal syndromes have genitourinary malformations within their clinical phenotype including the 18q-syndrome. Therefore, it is likely that a gene involved in genitourinary development maps to 18q. Recently, we have described a patient with an apparently balanced t(1;18)(q32;q22) karyotype with genitourinary malformations that are also observed in the 18q- syndrome. Clinical features in this patient include hypospadias, micropenis, and a labialized scrotum. We are testing the hypothesis that expression of a gene at or near the translocated breakpoint on chromosome 18 is disrupted by the translocation. A detailed physical map composed of BAC clones around the translocation breakpoint has been generated. Numerous ESTs that have been mapped to 18q21.3-q22.3 by the International Radiation Hybrid Consortium have been mapped relative to the translocation breakpoint and the BAC clones. Several candidate genes have been identified by this EST mapping. One gene produces two transcripts of 4.4kb and 7kb in size that differ by the length of their 3′ untranslated region. This gene is expressed in testes as well as in other tissues and has previously been described as the human equivelent of the chicken cadherin 7 gene. Another cDNA that shows homology to OB-cadherin maps in the same vicinity as the cadherin 7 gene. Therefore, it appears that a cluster of cadherin genes maps near the site of the translocation breakpoint. Experiments are currently in progress to characterize this gene cluster and to investigate the role of these genes in genitourinary development.
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Overhauser, J., Frizell, E., Dolsky, R. et al. Identification of candidate genes involved in genitourinary malformations. Genet Med 1, 48 (1999). https://doi.org/10.1097/00125817-199901000-00030
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DOI: https://doi.org/10.1097/00125817-199901000-00030