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Genetics of agenesis/hypoplasia of the uterus and vagina: narrowing down the number of candidate genes for Mayer-Rokitansky-Küster-Hauser Syndrome
- Source :
- Hum Genet
- Publication Year :
- 2020
-
Abstract
- PURPOSE: Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome consists of congenital absence of the uterus and vagina and is often associated with renal, skeletal, cardiac, and auditory defects. The genetic basis is largely unknown except for rare variants in several genes. Many candidate genes have been suggested by mouse models and human studies. The purpose of this study was to narrow down the number of candidate genes. METHODS: Whole exome sequencing was performed on 111 unrelated individuals with MRKH; variant analysis focused on 72 genes suggested by mouse models, human studies of physiological candidates, or located near translocation breakpoints in t(3;16). Candidate variants (CV) predicted to be deleterious were confirmed by Sanger sequencing. RESULTS: Sanger sequencing verified 54 heterozygous CV from genes identified through mouse (13 CV in 6 genes), human (22 CV in seven genes), and translocation breakpoint (19 CV in 11 genes) studies. Twelve patients had ≥ 2 CVs, including four patients with two variants in the same gene. One likely digenic combination of LAMC1 and MMP14 was identified. CONCLUSION: We narrowed 72 candidate genes to 10 genes that appear more likely implicated. These candidate genes will require further investigation to elucidate their role in the development of MRKH.
- Subjects :
- Male
Candidate gene
46, XX Disorders of Sex Development
Translocation Breakpoint
Chromosomal translocation
Biology
Translocation, Genetic
Article
Congenital Abnormalities
03 medical and health sciences
symbols.namesake
Mice
Exome Sequencing
Genetics
Animals
Humans
Gene
Mullerian Ducts
Genetics (clinical)
Exome sequencing
030304 developmental biology
Sanger sequencing
0303 health sciences
030305 genetics & heredity
Breakpoint
Uterus
Genetic Variation
Human genetics
Vagina
symbols
Female
Subjects
Details
- ISSN :
- 14321203
- Volume :
- 140
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Human genetics
- Accession number :
- edsair.doi.dedup.....916da3560a481c5b164cb2ceb40c254c