Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in 
the TRIM37 gene encoding a protein of unknown function. More than half of female 
patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex 
cord-stromal origin. In this work, we characterize the gynecological tumors of 
female patients with Mulibrey nanism in detail. In addition to tumors of the 
fibrothecoma group, 18% (4/22) of the patients were observed with epithelial 
neoplasias, including 2 ovarian adenofibromas, 1 ovarian poorly differentiated 
adenocarcinoma and 1 endometrial adenocarcinoma. To investigate the possible 
involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, 
we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts 
and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. No 
mutations in the open-reading frame of TRIM37 were detected. Two alternatively 
spliced variants were found, one lacking exon 23 and one exon 2. TRIM37del2 was 
also found in normal ovary but in a proportion of sporadic fibrothecomas, the 
TRIM37del2:TRIM37 ratio was increased. In normal ovary, TRIM37 was localized in 
the cytoplasm of stromal cells, especially theca cells surrounding developing 
follicles. TRIM37 transcript was found in all sporadic fibrothecomas examined, 
but 80% (20/25) of the tumors showed reduced or absent expression of TRIM37 
protein. Allelic loss at the TRIM37 locus (17q22-23) was observed in 6% of 
sporadic fibrothecomas. Nearly half of the sporadic fibrothecomas showed 
evidence of CpG promoter methylation, suggesting promoter downregulation as one 
mechanism of reduced TRIM37 expression. In conclusion, inherited biallelic 
inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and 
epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in 
the pathogenesis of sporadic fibrothecomas.