Persistent Mullerian duct syndrome caused by both a 27-bp deletion and a novel splice mutation in the MIS type II receptor gene
Article first published online: 3 OCT 2003
Copyright © 2003 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 67, Issue 10, pages 868–874, October 2003
How to Cite
Hoshiya, M., Christian, B. P., Cromie, W. J., Kim, H., Zhan, Y., MacLaughlin, D. T. and Donahoe, P. K. (2003), Persistent Mullerian duct syndrome caused by both a 27-bp deletion and a novel splice mutation in the MIS type II receptor gene. Birth Defects Research Part A: Clinical and Molecular Teratology, 67: 868–874. doi: 10.1002/bdra.10091
- Issue published online: 14 OCT 2003
- Article first published online: 3 OCT 2003
- Manuscript Accepted: 12 JUN 2003
- Manuscript Received: 25 NOV 2002
- National Institutes of Health, National Cancer Institute. Grant Number: CA 17393
- National Institute of Child Health and Human Development. Grant Number: HD 32112
Persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism that is characterized by the persistence of Mullerian derivatives in otherwise normally virilized males. Mutations of the Mullerian inhibiting substance (MIS) gene or the MIS type II receptor (MISRII) gene have been identified in PMDS patients with autosomal recessive transmission. We analyzed a compound heterozygote PMDS patient who had a 27-bp deletion in exon 10 in one allele and a novel mutation in intron 5 in the other allele of the MISRII gene.
Whole blood and tissue samples were obtained from a one-month-old 46,XY male with persistent PMDS and the MISRII gene was sequenced and compared to his mother's genomic DNA and that of 22 normal individuals. Serum MIS and the reproductive hormones were measured by standard immunoassays.
The patient's hormone levels were normal but the gene for MISRII contained several mutations, a 27-bp deletion in exon 10 on one allele (one of the most common mutations in PMDS) and a novel mutation in intron 5 in the other allele that altered splicing, resulting in retention of the intron and a frameshift, introducing a stop codon. Other mutations in introns 6 and 9 and in exon 11 might not be functionally significant.
This case reveals a novel mutation in the MISRII gene involving intronic sequences, which when coexisting with the already identified 27-bp deletion in exon 10, leads to PMDS. Birth Defects Research (Part A), 2003. © 2003 Wiley-Liss, Inc.