Is there a Mendelian transmission ratio distortion of the c.429_452dup(24bp) polyalanine tract ARX mutation?
Open accessAbstract
Intellectual disability is common. Aristaless-related homeobox (ARX) gene is one of the most frequently mutated and pleiotropic genes, implicated in 10 different phenotypes. More than half of ~100 reported cases with ARX mutations are due to a recurrent duplication of 24 bp, c.429_452dup, which leads to polyalanine tract expansion. The excess of affected males among the offspring of the obligate carrier females raised the possibility of transmission ratio distortion for the c.429_452dup mutation. We found a significant deviation from the expected Mendelian 1:1 ratio of transmission in favour of the c.429_452dup ARX mutation. We hypothesise that the preferential transmission of the c.429_452dup mutation may be due to asymmetry of meiosis in the oocyte. Our findings may have implications for genetic counselling of families segregating the c.429_452dup mutation and allude to putative role of ARX in oocyte biology.
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About 5% of DM1 individuals also have ASD.
“Approximately 5% of individuals with DM1 also have ASD45,46.”
From Genome-wide detection of tandem DNA repeats that are expanded in autism (2020) · cites this paper as [45]
The unbiased approach confirmed a previously indicated ASD-DMPK tandem repeat expansion association.
“Thus, our independent, unbiased approach confirmed a previously indicated association between ASD and DMPK tandem repeat expansions45,46.”
From Genome-wide detection of tandem DNA repeats that are expanded in autism (2020) · cites this paper as [45]
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- Authors
- Shoubridge, C., Gardner, A., Schwartz, C. E., Hackett, A., Field, M., & Gecz, J.
- Affiliations
- South Australia Pathology (AU)
- Greenwood Genetic Center (US)
- Hunter Genetics (AU)
- Corresponding author
- Shoubridge, Cheryl
- Venue
- European Journal of Human Genetics
- Published
- 2012-04-11
- Volume
- 20
- Issue
- 12
- Pages
- 1311-1314
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC3499743
- OpenAlex
- W1996507669
- Cited by
- 10
- References
- 51
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2016: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Institutes of Health (5r01hd026202-15)
- National Health and Medical Research Council (400121)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD026202, HD 26202)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- ARX gene, polyalanine tract expansion, segregation distortion, intellectual disability, sex ratio distortion, genetic counseling, oocyte biology
- MeSH terms
- Alanine, Female, Heterozygote, Humans, Male, Meiosis, Mutation, Oocytes, Pedigree, Repetitive Sequences, Nucleic Acid, Transcription Factors, Homeodomain Proteins, Inheritance Patterns
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