A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces
We report on three Aboriginal Australian siblings with a unique phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome. A gain-of-function mutation in MTOR was identified and represents the first reported human condition due to a germline, familial...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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John Wiley & Sons, Inc.
2015
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/3184 |
| _version_ | 1848744161805598720 |
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| author | Baynam, G. Overkov, A. Davis, M. Mina, K. Schofield, L. Allcock, R. Laing, N. Cook, M. Dawkins, Hugh Goldblatt, J. |
| author_facet | Baynam, G. Overkov, A. Davis, M. Mina, K. Schofield, L. Allcock, R. Laing, N. Cook, M. Dawkins, Hugh Goldblatt, J. |
| author_sort | Baynam, G. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | We report on three Aboriginal Australian siblings with a unique phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome. A gain-of-function mutation in MTOR was identified and represents the first reported human condition due to a germline, familial MTOR mutation. We describe the findings in this family to highlight that (i) the path to determination of pathogenicity was confounded by the lack of genomic reference data for Australian Aboriginals and that (ii) the disease biology, functional analyses in this family, and studies on the tuberous sclerosis complex support consideration of an mTOR inhibitor as a therapeutic agent. |
| first_indexed | 2025-11-14T05:57:04Z |
| format | Journal Article |
| id | curtin-20.500.11937-3184 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T05:57:04Z |
| publishDate | 2015 |
| publisher | John Wiley & Sons, Inc. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-31842017-09-13T14:31:38Z A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces Baynam, G. Overkov, A. Davis, M. Mina, K. Schofield, L. Allcock, R. Laing, N. Cook, M. Dawkins, Hugh Goldblatt, J. megalencephaly mTOR indigenous rapamycin repurposing Aboriginal RASopathy We report on three Aboriginal Australian siblings with a unique phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome. A gain-of-function mutation in MTOR was identified and represents the first reported human condition due to a germline, familial MTOR mutation. We describe the findings in this family to highlight that (i) the path to determination of pathogenicity was confounded by the lack of genomic reference data for Australian Aboriginals and that (ii) the disease biology, functional analyses in this family, and studies on the tuberous sclerosis complex support consideration of an mTOR inhibitor as a therapeutic agent. 2015 Journal Article http://hdl.handle.net/20.500.11937/3184 10.1002/ajmg.a.37070 John Wiley & Sons, Inc. restricted |
| spellingShingle | megalencephaly mTOR indigenous rapamycin repurposing Aboriginal RASopathy Baynam, G. Overkov, A. Davis, M. Mina, K. Schofield, L. Allcock, R. Laing, N. Cook, M. Dawkins, Hugh Goldblatt, J. A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces |
| title | A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces |
| title_full | A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces |
| title_fullStr | A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces |
| title_full_unstemmed | A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces |
| title_short | A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces |
| title_sort | germline mtor mutation in aboriginal australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces |
| topic | megalencephaly mTOR indigenous rapamycin repurposing Aboriginal RASopathy |
| url | http://hdl.handle.net/20.500.11937/3184 |