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| Mendeliome v1.4625 | PITX1 upstream regulatory region |
Sarah Milton Region: PITX1 upstream regulatory region was added Region: PITX1 upstream regulatory region was added to Mendeliome. Sources: Literature Mode of inheritance for Region: PITX1 upstream regulatory region was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for Region: PITX1 upstream regulatory region were set to PMID: 30711920; 23022097; 25124102; 23587911 Phenotypes for Region: PITX1 upstream regulatory region were set to Liebenberg syndrome, MIM#186550 Review for Region: PITX1 upstream regulatory region was set to GREEN Added comment: PITX1 is a transcription factor expressed solely in the hindlimb during limb development where it ensures proper outgrowth and patterning of this tissue. Over 25 individuals have been reported in the literature with deletions upstream of PITX1 presenting with Liebenberg syndrome characterised by dysplastic elbow joints and the fusion of wrist bones and the consequent radial deviation. With upper limb features resembling some of those seen in the lower limb. The deletions seen in affected individuals range from 8kb to 134kb in size and are thought to result in overexpression of PITX1 by affecting the proximity between the coding sequence and an upstream enhancer (referred to variably as 'Pen' or 'hs1473'). The deletion removes part of a different protein coding gene - MACROH2A1 which is not thought to contribute to the pathogenesis (knockout mice do not present with a similar phenotype to Liebenberg). Authors of PMID: 30711920 suggest the promoter of MACROH2A1 acts as an insulator between the upstream enhancer and PITX1 however further functional studies are required to establish this. Functional studies involving transgenic mice with the enhancer element just upstream of PITX1 resulting in a similar phenotype to affected individuals. Note: Maximal reported deletion coordinates at time of writing: chr5:135288912-135423802 Minimum: chr5:135393716-135402219: Sources: Literature |
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