Back to Search
Start Over
A Novel Missense Mutation 224G>T (R75M) in SRY Coding Region Interferes with Nuclear Import and Results in 46, XY Complete Gonadal Dysgenesis
- Source :
- PLoS ONE, PLoS ONE, Vol 11, Iss 12, p e0168484 (2016)
- Publication Year :
- 2016
- Publisher :
- Public Library of Science, 2016.
-
Abstract
- SRY-mutation-caused sex reversal is a rare disease and mostly associated with a de novo mutation since the patients with defective SRY is infertile. There are many reports about SRY-mutation associated 46, XY ovarian disorder of sex development (DSD), but few described their molecular mechanism. Here we report a de novo mutation 224G>T (R75M) in SRY associated with a phenotypic female, 46, XY karyotype and dysgerminoma. The wild and mutated SRY were cloned into recombinant plasmid and expressed in cells in vitro, the result showed the mutated SRY is greatly accumulated in cytoplasm while the wild type SRY is mostly localized in nucleus. To make sure no other genes were involved, we performed the trio-based whole exome sequencing using the DNA samples from the proband and the parents, and no mutations were identified especially in DHH, NR0B1, NR5A1, SOX9 and MAP3K1, indicating the de novo mutation in SRY is the single defect responsible for the female sex reversal. We also used bioinformatics simulation analysis to predict impact of the mutation on SRY function, and find the R75 in wild type SRY can form a hydrogen bond with serine at 91 (S91) that make the SRY protein well fit into the minor groove of target DNA, while the M75 in the mutated SRY can’t. Finally, we reviewed SRY mutations based on the available references and analyzed the mutation distribution patterns according to density and continuity, which may be useful for further study of the SRY structure, function, and its relatedness with DSD.
- Subjects :
- 0301 basic medicine
Confocal Microscopy
Molecular biology
Gene Identification and Analysis
Gonadal dysgenesis
lcsh:Medicine
030105 genetics & heredity
medicine.disease_cause
Sequencing techniques
Missense mutation
DNA sequencing
lcsh:Science
Frameshift Mutation
health care economics and organizations
Genetics
Gonadal Dysgenesis, 46,XY
Mutation
Microscopy
Multidisciplinary
Light Microscopy
Nonsense Mutation
Sex reversal
Testis determining factor
population characteristics
Female
geographic locations
Research Article
Adult
Missense Mutation
Nonsense mutation
Active Transport, Cell Nucleus
Mutation, Missense
Biology
Research and Analysis Methods
Frameshift mutation
03 medical and health sciences
Open Reading Frames
Young Adult
parasitic diseases
medicine
Point Mutation
Humans
Mutation Detection
Point mutation
lcsh:R
Biology and Life Sciences
social sciences
medicine.disease
Sex-Determining Region Y Protein
030104 developmental biology
Molecular biology techniques
lcsh:Q
Confocal Laser Microscopy
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....b96f23aea9bfa050846a8fe08c1af86a