Activity
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15 actions
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| Intellectual disability v7.41 | SOX9 |
Achchuthan Shanmugasundram Tag Q2_24_demote_amber was removed from gene: SOX9. Tag Q2_24_NHS_review was removed from gene: SOX9. |
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| Intellectual disability v7.41 | SOX9 | Achchuthan Shanmugasundram reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v7.40 | SOX9 |
Achchuthan Shanmugasundram Source Expert Review Amber was added to SOX9. Source NHS GMS was added to SOX9. Rating Changed from Green List (high evidence) to Amber List (moderate evidence) |
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| Intellectual disability v6.40 | SOX9 |
Sarah Leigh Tag Q2_24_demote_amber tag was added to gene: SOX9. Tag Q2_24_NHS_review tag was added to gene: SOX9. |
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| Intellectual disability v6.40 | SOX9 | Sarah Leigh reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v6.40 | SOX9 | Sarah Leigh Phenotypes for gene: SOX9 were changed from Campomelic dysplasia with autosomal sex reversal, 114290; Acampomelic campomelic dysplasia, 114290; Campomelic dysplasia, 114290; intellectual disability to Campomelic dysplasia with autosomal sex reversal, OMIM:114290; Acampomelic campomelic dysplasia, OMIM:114290; Campomelic dysplasia, OMIM:114290; campomelic dysplasia, MONDO:0007251 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v5.497 | SOX9 | Tracy Lester reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.597 | SOX4 |
Konstantinos Varvagiannis gene: SOX4 was added gene: SOX4 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SOX4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SOX4 were set to Global developmental delay; Intellectual disability; Growth delay; Clinodactyly of the 5th finger; Abnormality of head or neck Penetrance for gene: SOX4 were set to unknown Review for gene: SOX4 was set to GREEN Added comment: Zawerton et al. (DDD study among the co-authors - doi.org/10.1016/j.ajhg.2018.12.014 - PMID:NA) report on 4 unrelated individuals with de novo SOX4 pathogenic variants. The common phenotype consisted of DD/ID (4/4 - very mild to severe), overlapping facial features as well as digital anomalies (5th finger clinodactyly in 4/4). SOX4 is a member of the SOX family of transcription factors, all presenting at least 50% identity with SRY (the first identified member of this family) in the HMG (DNA-binding) domain. Most SOX genes have important roles in cell fate / differentiation. Mutations in other genes of this family (eg. SRY, SOX9, SOX10, SOX5) are associated with severe human syndromes. SOX4 is highly expressed in human brain during gestation - particularly in areas of active neurogenesis - with progressive decrease thereafter until the 3rd - 4th decade of life. Knockdown of the SOX4 ortholog in Xenopus laevis embryos resulted in smaller head size, microphthalmia, shorter body length and underdevelopment of fore- and mid-brain. (Growth deficiency was a common feature in affected individuals, and microcephaly in 2/4). Sox4-null mice die in utero due to heart septation defects, while such abnormalities were not reported in heterozygous mice. One affected subject had a VSD. Sox4 inactivation in mice results in impaired skeletal growth (similarly to the patients). All 4 different missense variants clustered in the HMG domain (aa 58-133) which appears relatively (more) depleted in missense variants (only 12 missense HMG-domain variants in gnomAD). [Overall the Z-score for missense variants is 3.72. pLI = 0.38. %HI in DECIPHER : 24.67%]. The 4 missense variants presented impaired DNA binding and transcription activation in COS-1 transfected cells which appeared to distinguish them from the 12 gnomAD ones. Synthesis, stability and nuclear translocation appeared to be similar to wt. Other parameters eg. residue conservation in the SOX family, presence of "equivalent" known disease causing mutations in other SOX genes or in silico analyses suggesting structural consequences were supportive of a deleterious effect for the 4 variants (but also for some of the 12 gnomAD ones). SOX4 and SOX11 have almost identical DNA-binding domains, while the mechanism of mutations reported and the phenotypes appear to be relatively similar, as commented by the authors. -------------- SOX4 is not associated with any phenotype in G2P, nor in OMIM. This gene is not - at least commonly - included in gene panels for ID offered by diagnostic laboratories. -------------- As a result SOX4 can be considered for inclusion in the ID panel as green (or amber). Sources: Literature |
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| Intellectual disability | SOX9 | Louise Daugherty classified SOX9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | SOX9 | Louise Daugherty classified SOX9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | SOX9 | Rachel Jones reviewed SOX9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | SOX9 | BRIDGE consortium edited their review of SOX9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | SOX9 | Louise Daugherty classified SOX9 as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | SOX9 | Louise Daugherty commented on SOX9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability | SOX9 | BRIDGE consortium reviewed SOX9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||