TY - JOUR
T1 - A Germline MTOR Mutation in Aboriginal Australian Siblings with Intellectual Disability, Dysmorphism, Macrocephaly, and Small Thoraces
AU - Baynam, Gareth
AU - Overkov, A.
AU - Davis, Mark
AU - Mina, Kym
AU - Schofield, L.
AU - Allcock, Richard
AU - Laing, Nigel
AU - Cook, M.
AU - Dawkins, Hugh
AU - Goldblatt, Jack
PY - 2015
Y1 - 2015
N2 - © 2015 Wiley Periodicals, Inc. 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.
AB - © 2015 Wiley Periodicals, Inc. 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.
U2 - 10.1002/ajmg.a.37070
DO - 10.1002/ajmg.a.37070
M3 - Article
C2 - 25851998
SN - 1552-4825
VL - 167
SP - 1659
EP - 1667
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 7
ER -
