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| Mendeliome v2.393 | HOXD cluster regulatory region | Sarah Milton Marked Region: HOXD cluster regulatory region as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.393 | HOXD cluster regulatory region | Sarah Milton Region: hoxd cluster regulatory region has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.393 | HOXD cluster regulatory region | Sarah Milton Classified Region: HOXD cluster regulatory region as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.393 | HOXD cluster regulatory region | Sarah Milton Region: hoxd cluster regulatory region has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.392 | HOXD cluster regulatory region |
Sarah Milton changed review comment from: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds. Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints. Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region. The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression. It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes. Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb. This is thought to occur as each enhancer region normally acts on different precursor cells in normal physiology thus rearranging the region results in misexpression. Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication). Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype. Sources: Literature; to: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds. Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints. Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region. The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression. It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes. Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb. This is thought to occur as each enhancer region acts on different precursor cells in normal physiology thus rearranging the region results in misexpression. Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication). Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype. Sources: Literature |
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| Mendeliome v2.392 | HOXD cluster regulatory region |
Sarah Milton changed review comment from: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds. Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints. Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region. The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression. It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes. Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb. This is thought to occur as each enhancer region normally acts on different precursor cells but repositioning of genes in the region results in misexpression. Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication). Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype. Sources: Literature; to: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds. Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints. Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region. The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression. It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes. Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb. This is thought to occur as each enhancer region normally acts on different precursor cells in normal physiology thus rearranging the region results in misexpression. Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication). Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype. Sources: Literature |
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| Mendeliome v2.392 | HOXD cluster regulatory region |
Sarah Milton Region: HOXD cluster regulatory region was added Region: HOXD cluster regulatory region was added to Mendeliome. Sources: Literature regulatory region tags were added to Region: HOXD cluster regulatory region. Mode of inheritance for Region: HOXD cluster regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for Region: HOXD cluster regulatory region were set to 20648051; 36990510; 34408147; 31591517; 20577005; 29517766 Phenotypes for Region: HOXD cluster regulatory region were set to Mesomelic dysplasia, Kantaputra type, MIM#156232 Review for Region: HOXD cluster regulatory region was set to GREEN Added comment: The HOXD cluster of genes including HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12, HOXD13 are involved in embryonic patterning in developing limb buds. Multiple publications report copy number changes in the 2q31 region involving the HOXD cluster resulting in Mesomelic dysplasia, Kantaputra type characterised by marked shortening of the upper and lower limbs and progressive flexion contractures of PIP joints. Copy number changes in affected individuals included deletions, duplications and inversions ranging from 93kb to 1mb, many individuals had more than one structural variant within the region. The proposed molecular mechanism is repositioning of the HOX genes in relation to up and downstream enhancers resulting in misexpression. It should be noted deletions of the HOX gene cluster don't recapitulate the phenotype as it is thought there is compensation from HOXA genes. Functional studies in a mouse model showed inappropriate expression of HOXD13 in the middle segment of limb (ulnar/radius/tibia/fibula) and loss of normal expression in hand/foot, as well as loss of normal HOXD11 expression in the middle segment of the limb. This is thought to occur as each enhancer region normally acts on different precursor cells but repositioning of genes in the region results in misexpression. Note: coordinates used for the above entry were the minimum seen in an affected individual (duplication). Authors of above publications did note if the copy number variant is too large it did not recapitulate the phenotype. Sources: Literature |
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