• PMID: 14745940
• Gene Name: MIS
• Condition: Persistent Mullerian duct syndrome
• Association: 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.
• Mutation: 27-bp deletion in exon 10 in one allele and a novel mutation in intron 5 in the other allele of the MISRII gene
• Population size: 23
• Population details: 23 (1 46,XY male with persistent PMDS, 22 normal individuals)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Persistent Mullerian duct syndrome

Persistent Mullerian duct syndrome caused by both a 27-bp deletion and a novel splice mutation in the MIS type II receptor gene

Hoshiya M, Christian BP, Cromie WJ, Kim H, Zhan Y, MacLaughlin DT, Donahoe PK.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CI - Copyright 2003 Wiley-Liss, Inc. FAU - Hoshiya, Makiko AU - Hoshiya M AD - Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. FAU - Christian, Benjamin P AU - Christian BP FAU - Cromie, William J AU - Cromie WJ FAU - Kim, Hyung AU - Kim H FAU - Zhan, Yong AU - Zhan Y FAU - MacLaughlin, David T AU - MacLaughlin DT