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| Osteogenesis imperfecta v2.6 | MESD |
Eleanor Williams changed review comment from: Gene suggested by Alistair Pagnamenta. Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM. PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking. Sources: Literature; to: Gene suggested by Alistair Pagnamenta. Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM. PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking. Alistair Pagnamenta notes that there is a lack of sibling data. |
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| Osteogenesis imperfecta v2.4 | MESD |
Eleanor Williams gene: MESD was added gene: MESD was added to Osteogenesis imperfecta. Sources: Literature Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESD were set to 31564437 Added comment: Gene suggested by Alistair Pagnamenta. Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM. PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking. Sources: Literature |
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