A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces. (6th April 2015)

• Record Type: Journal Article
• Authors: Baynam, Gareth; Overkov, Angela; Davis, Mark; Mina, Kym; Schofield, Lyn; Allcock, Richard; Laing, Nigel; Cook, Matthew; Dawkins, Hugh; Goldblatt, Jack
• Is Part Of: American journal of medical genetics. Volume 167:Number 7(2015:Jul.)
• Page Start: 1659
• Page End: 1667
• Publication Date: 2015-04-06
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37070
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga37070-sec-0001" sec-type="section"> <p>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 <italic>MTOR</italic> was identified and represents the first reported human condition due to a germline, familial <italic>MTOR</italic> 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 Wiley Periodicals, Inc.</p> </sec> </abstract>