Finding cures for children's genetic diseases


Major Achievements

2012    Unique Australian eye disease family found to have a novel mutation in TUBB2B. The eye and brain phenotype in this family pinpointed the divergent roles of ß-tubulin subtypes in microtubule dynamics and axon guidance.  Article.
2013    Whole exome sequencing successful for disease gene identification in developmental eye disease. These eye disorders are markedly genetically heterogeneous, and our study demonstrated the value of whole exome sequencing for genetic diagnosis in these conditions. Article.
2014     Australian families with balanced structural variants lead to novel candidate disease gene identification in cerebral and other disorders. A mate paired whole genome sequencing strategy was undertaken with our Genome Institute of Singapore collaborators, and novel candidate disease genes identified that may contribute to schizencephaly and developmental delay. (Article: Utami KH, Hillmer AM, Aksoy I, Chew EGY, Teo ASM, Zhang Z, Lee CWH, Chen PJ, Chan CS, Ariyaratne PN, Rouam SL, Soo LS, Yousoof S, Prokudin I, Peters G, Collins F, Wilson M, Kakakios A, Haddad G, Menuet A, Perche O, Hong ST, Sung KW, Ruan X, Ruan Y, Liu ET, Briault S, Jamieson RV, Davila S, Cacheux V.   Detection of chromosomal breakpoints in patients with developmental delay and speech disorders.  PLoS One. 2014 Mar 6;9(3):e90852.  PMID:  24603971)

2015    SIPA1L3 novel disease gene identification and characterisation. Human, zebrafish and mouse studies showed that SIPA1L3 has a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organisation. [hyperlink to article: Greenlees R*, Mihelec M*, Yousoof S*, Speidel D, Wu SK, Rinkwitz S, Prokudin I, Perveen R, Cheng A, Ma A, Nash B, Gillespie R, Loebel DA, Clayton-Smith J, Lloyd IC, Grigg JR, Tam PP, Yap AS, Becker TS, Black GC, Semina E, Jamieson RV.  Mutations in SIPA1L3 cause eye defects through disruption of cell polarity and cytoskeleton organization. (*Equal first authors)   Human Molecular Genetics, 2015; 24(20): 5789-5804.  PMID: 26231217]

2016    Australian-first of translation of our research genomic testing for genetic eye diseases to clinical diagnostic testing, through our collaboration with the Sydney Genome Diagnostics Laboratory within the Western Sydney Genetics Program at The Children’s Hospital at Westmead. As we head to the new era of genetic therapies for some of these conditions, attainment of genetic diagnoses for patients is critical. For most of the new clinical trials or therapies, patients are required to have a genetic diagnosis to be eligible for the therapy [link to example articles: 
Ma AS, Grigg JR, Ho G, Prokudin I , Farnsworth E, Holman K, Cheng A, Billson FA, Martin F, Fraser C, Mowat D, Smith J, Christodoulou J, Flaherty M, Bennetts B, Jamieson RV.  Sporadic and familial congenital cataracts: mutational spectrum and new diagnoses using next-generation sequencing. Human Mutation, 2016 Apr;37(4):371-84. PMID:  26694549; 
Nash BM, Symes R, Goel H, Dinger ME, Bennetts B, Grigg JR, Jamieson RV. NMNAT1 variants cause cone and cone-rod dystrophy. European Journal of Human Genetics, 2018, Mar;26(3):428-433. Epub 2017 Nov 28. PMID: 29184169]

2019    ALPK1 novel retinal disease gene identification and characterisation. The first to report a newly defined retinal dystrophy syndrome and its causative disease gene ALPK1, opening up a new disease mechanism pathway. [link to article: Williams LB#, Javed A#, Sabri A#, Morgan DJ#, Huff CD, Grigg JR, Ting Heng X, Khng A, Hollink IHIM, Morrison MA, Owen LA, Anderson K, Kinard K, Greenlees R, Novacic D, Sen HN, Zein WM, Rodgers G, Vitale AT, Haider NB, Hillmer AM, Ng PC, Shankaracharya, Cheng A, Zheng L, Gillies M, von Slegtenhorst M, van Hagen PM, Missotten TOAR, Farley GL, Polo M, Malatack J, Curtin J, Martin F, Arbuckle S, Alexander SI, Chircop M, Davila S, Digre K, Jamieson RV##, DeAngelis MM##  ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. # Equal First Authors; ##Equal Last Authors,  Genetics in Medicine, 2019, Sep;21(9):2103-2115. Epub 2019 Apr 10. PMID: 30967659]

2020    A multidisciplinary team (MDT) approach encompassing phenotypic, genomic, variant, and segregation analysis to maximise the genomic diagnostic rate. [Ma AS, Yousoof S, Grigg JR, Flaherty M, Minoche AE, Cowley M, Nash BM, Ho G, Gayagay T, Lai T, Farnsworth E, Hackett EL, Fisk K, Wong K, Holman KJ, Jenkins G, Cheng A, Martin F, Karaconji T, Elder JE, Enriquez A, Wilson M, Amor D, Stutterd CA, Kamien B, Nelson J, Dinger ME, Bennetts B, Jamieson RV.  Revealing hidden genetic diagnoses in the ocular anterior segment disorders. Genetics in Medicine, 2020, Jun 5. PMID: 32499604.