ArticleGenetics in medicine : official journal of the American College of Medical Genetics2017
Autozygosity reveals recessive mutations and novel mechanisms in dominant genes: implications in variant interpretation.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 55 papers, 1 of them a synthesis that pooled it.
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55 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
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- Genomics of rare diseases in the Greater Middle East.Nature genetics · 2025Review
- Clinical application of next generation sequencing for Mendelian disease diagnosis in the Iranian population.NPJ genomic medicine · 2024Article
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- Tissue-specific macrophages: how they develop and choreograph tissue biology.Nature reviews. Immunology · 2023Review
- Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families.Nature communications · 2023Article
- The Role of Tumor Epithelial-Mesenchymal Transition and Macrophage Crosstalk in Cancer Progression.Current osteoporosis reports · 2023Review
- Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria.Human molecular genetics · 2023Article
- Heterogeneity in biomarkers, mitogenome and genetic disorders of the Arab population with special emphasis on large-scale whole-exome sequencing.Archives of medical science : AMS · 2023Article
- Homozygous mutation inBioImpacts : BI · 2023Article
- Autosomal Recessive ACTG2-Related Visceral Myopathy in Brothers.JPGN reports · 2022Article
- Modeling CSF-1 receptor deficiency diseases - how close are we?The FEBS journal · 2022Review
- Dominant-acting CSF1R variants cause microglial depletion and altered astrocytic phenotype in zebrafish and adult-onset leukodystrophy.Acta neuropathologica · 2022Article
- Dysosteosclerosis: Clinical and Radiological Evolution Reflecting Genetic Heterogeneity.JBMR plus · 2022Article
- Robots as models of evolving systems.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of this study is to describe recessive alleles in strictly dominant genes. Identifying recessive mutations in genes for which only dominant disease or risk alleles have been reported can expand our understanding of the medical relevance of these genes both phenotypically and mechanistically. The Saudi population is enriched for autozygosity, which enhances the homozygous occurrence of alleles, including pathogenic alleles in genes that have been associated only with a dominant inheritance pattern.
methodsExome sequencing of patients from consanguineous families with likely recessive phenotypes was performed. In one family, the genotype of the deceased children was inferred from their parents due to lack of available samples.
resultsWe describe the identification of 11 recessive variants (5 of which are reported here for the first time) in 11 genes for which only dominant disease or risk alleles have been reported. The observed phenotypes for these recessive variants were novel (e.g., FBN2-related myopathy and CSF1R-related brain malformation and osteopetrosis), typical (e.g., ACTG2-related visceral myopathy), or an apparently healthy state (e.g., PDE11A), consistent with the corresponding mouse knockout phenotypes.
conclusionOur results show that, in the era of genomic sequencing and "reverse phenotyping," recessive variants in dominant genes should not be dismissed based on perceived "incompatibility" with the patient's phenotype before careful consideration.Genet Med advance online publication 06 April 2017.
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