Related Experiment Video
Updated: Aug 29, 2026
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Persistent Mullerian duct syndrome caused by both a 27-bp deletion and a novel splice mutation in the MIS type II
Makiko Hoshiya1, Benjamin P Christian, William J Cromie
1Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
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.
Insights
Persistent Mullerian duct syndrome (PMDS) in a male infant was linked to a novel mutation in the MISRII gene. This genetic finding, involving intronic sequences, helps explain the rare condition of male pseudohermaphroditism.
Area of Science:
- Genetics
- Endocrinology
- Reproductive Biology
Background:
- Persistent Mullerian duct syndrome (PMDS) is a rare genetic disorder causing male pseudohermaphroditism.
- It involves the persistence of Mullerian duct derivatives in genetically male individuals.
- Mutations in the Mullerian inhibiting substance (MIS) or its type II receptor (MISRII) gene are implicated in autosomal recessive PMDS.
Purpose of the Study:
- To investigate the genetic basis of PMDS in a compound heterozygote patient.
- To identify novel mutations in the MISRII gene associated with PMDS.
- To understand the molecular mechanisms leading to PMDS.
Main Methods:
- Genetic sequencing of the MISRII gene in a PMDS patient and comparison with parental DNA.
- Analysis of whole blood and tissue samples.
- Measurement of serum MIS and reproductive hormones using immunoassays.
Main Results:
- The patient presented with normal hormone levels but carried two MISRII gene mutations.
- A common 27-bp deletion in exon 10 was identified on one allele.
- A novel mutation in intron 5 on the other allele caused altered splicing, intron retention, and a frameshift with a premature stop codon.
Conclusions:
- A novel intronic mutation in the MISRII gene, alongside a previously identified deletion, causes PMDS.
- This compound heterozygosity explains the patient's condition.
- The findings highlight the role of intronic mutations in PMDS pathogenesis.
Related Concept Videos
02:18Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
02:28Sex-linked Disorders
01:32RNA Splicing
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:21Nondisjunction
02:14Nondisjunction