Fraser syndrome: affected siblings born to nonconsanguineous parents and diagnosed at autopsy.

Fraser syndrome (MIM 219000) is a rare genetic disorder with major features including cryptophthalmos, syndactyly, and genital anomalies. We report 2 independently autopsied children of the same nonconsanguineous parents. The siblings exhibit similar clinical features, all of which are consistent with a diagnosis of Fraser syndrome. The gross and microscopic findings provide insight into the highly variable clinical presentation of Fraser syndrome. Molecular diagnostic studies of the index case failed to identify one of the known gene mutations in the FRAS1 and FREM2 genes associated with Fraser syndrome. This raises the possibility that other genes or undetected mutations in the FRAS1/FREM2 genes may cause Fraser syndrome.

Genomic organization of an intron-containing sperm protein 17 gene (Sp17-1) and an intronless pseudogene (Sp17-2) in humans: a new model.

Sp17 was initially thought to be a sperm specific protein involved in the interaction of the spermatozoon with the oocyte's surrounding extracellular glycoprotein matrix. Recent reports, however, indicate that Sp17 expression is neither testis-specific nor is it exclusively used for binding to the zona pellucida of the oocyte. In this study, we provide comprehensive characterization of the genomic structure of Sp17. We identified an intron-containing gene (Sp17-1) containing five exonic and four intronic sequences. Analysis of Sp17 transcripts using rapid amplification of DNA complementary to RNA (cDNA) ends (RACE) and polymerase chain reaction (PCR) techniques showed the presence of alternative polyadenylation resulting in the production of varying lengths of mRNAs as well as the usage of different transcriptional start sites. Moreover, an earlier description of the human Sp17 mRNA describing a splice variant could not be confirmed. Comparison to mouse Sp17 gene organization demonstrated a high degree of conservation, suggesting selective evolutionary pressure for this protein to retain a conserved gene architecture. Additionally, we identified a second gene (Sp17-2), whose most striking characteristic was the complete absence of introns. This Sp17-2 gene has likely arisen by reverse transcription (RT) of a spliced Sp17-1 mRNA with subsequent integration into the human genome. Its open reading frame (ORF) is interrupted by stop codons, giving rise to a pseudogene. Furthermore, Southern blot analysis of human genomic DNA indicated the possibility of additional Sp17 species within the human genome.

Characterization of sperm protein 17 in human somatic and neoplastic tissue.

Sperm protein 17 (Sp17) is a highly antigenic, testes-specific protein whose known function is to bind sperm to the zona pellucida. However, the Sp17 gene has been recently detected in normal non-testes tissues and malignant neoplasias. As the role of Sp17 in non-testes tissues is unknown, the characterization of the Sp17 gene in highly proliferating tissues may provide further insight into the regulation and alternative function of Sp17. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to amplify the Sp17-1 transcript in multiple normal human tissues and cancer cell lines. Similarly, the Sp17-2 gene was examined by PCR. In addition, Northern and Western blot analyses were used to detect Sp17 mRNA and protein expression. The Sp17-1a and Sp17-1b transcripts were amplified from cancer cell lines. Similarly, an Sp17-2 transcript was also detected in cancer cell lines. Furthermore, Northern blot analysis revealed Sp17 mRNA expression in all cancer cell lines examined. However, Sp17 protein expression was not detected. The differential detection of the Sp17 transcripts in cancer cell lines as compared to normal non-testes tissues, suggests a potential pathogenic role for Sp17 in diseased cells. Moreover, the Sp17-2 transcript may be a marker for highly proliferating cells. Collectively, these data implicate Sp17 as a cancer testis antigen.