Staff profile

Dr Danuta Z Loesch-Mdzewska

Senior Research Fellow

Faculty of Science, Technology and Engineering

School of Psychological Science
Department of Psychology

Biological Sciences Building 2, room 116., Melbourne (Bundoora)

 

Qualifications

B Med Surg, MD (clinical neurology); PhD (human genetics) Warsaw.

Membership of professional associations

Australasian Human Genetics Society, Human Biology Society, Croatian Anthropol Society, Am Assoc Advanc Sci.

Area of study

Genetics

Brief profile

 Before joining La Trobe University Dr Loesch worked as a clinical neurologist and, subsequently, as a clinician and researcher (Associate Professor) in the Department of Genetics, Institute of Neurology and Psychiatry, Warsaw, Poland, with several periods spent at the Galton Laboratory, University College London conducting research into human genetics supported by MRC, Lalor Foundation, and other grants.

In 1980 she was invited by the Australian Department of Education under the Australian-European Awards Programme to work at the RSBS, Australian National University. She joined the School of Genetics, and then Psychology, at La Trobe University in 1984, and has since been supported by the NHMRC (including the Fellowship), ARC, NIH (US), and other minor research grants. She has been conducting multidisciplinary studies of genotype-phenotype relationships in inherited conditions determined by unstable mutations (trinucleotide CGG repeat expansions), with special emphasis on the range of disorders caused by mutations in the Fragile X Mental Retardation 1 (FMR1) gene, from severe neurodevelopmental abnormality, Fragile X Syndrome, to late onset  progressive neurodegenerative disorders in the form of tremor/ataxia  and dementia. These studies have been possible through extensive collaborations with neurology clinics in Victoria, Tasmania and Queensland (access to study participants and tissue samples),  and research laboratories specialized in relevant  fields  including Murdoch Institute in melbourne, Eskitis Institute in Brisbane and Department of Biochemistry and Molecular Medicine at UC Davis. In recent years these studies led to characterization of the range of neurological and neuropsychological manifestations occuring in older carriers of  small CGG expansion FMR1 alleles, as well as to identification of the smallest expansion alleles as the commonest  genetic risk factor for Parkinson's disease. Moreover, the latest results revealed genetic and other molecular mechanisms (including mitochondrial dysfunction) underlying neurodegenerative process, and  these studies are continuing.

Research interests:

- genetic background and cellular pathology determining  neuropsychological and clinical changes in FMR1 gene (fragile X) - associated disorders, with special emphasis on late-onset neurogenerative conditions in aged  carriers of FMR1 premutation alleles and autism in children carrying premutation or full mutation FMR1 alleles.

Recent publications

1.Grigsby, J., Brega, A.G., Jacquemont, S., Loesch, D.Z., Leehey, M.A., Goodrich, G.K., Hagerman, R.J., Epstein, J., Wilson, R., Cogswell, J.B., et al. 2006. Impairment in the cognitive functioning of men with fragile X-associated tremor/ataxia syndrome (FXTAS). J Neurol Sci 248:227-33.

2.Cohen, S., Masyn, K., Adams, J., Hessl, D., Rivera, S., Tassone, F., Brunberg, J., DeCarli, C., Zhang, L., Cogswell, J., Loesch, D.Z., et al. 2006. Molecular and imaging correlates of the fragile X-associated tremor/ataxia syndrome. Neurology 67:1426-31.

3.Loesch, D.Z., Litewka, L., Churchyard, A., Gould, E., Tassone, F., and Cook, M. 2007. Tremor/ataxia syndrome and fragile X premutation: diagnostic caveats. J Clin Neurosci 14:245-8.

4.Loesch, D.Z., Bui, Q.M., Huggins, R.M., Mitchell, R.J., Hagerman, R.J., and Tassone, F. 2007. Transcript levels of the intermediate size or grey zone fragile X mental retardation 1 alleles are raised, and correlate with the number of CGG repeats. J Med Genet 44:200-4.

5.Loesch, D.Z., Cook, M., Litewka, L., Gould, E., Churchyard, A., Tassone, F., Slater, H.R., and Storey, E. 2008. A low symptomatic form of neurodegeneration in younger carriers of the FMR1 premutation, manifesting typical radiological changes. J Med Genet 45:179-81.

6.Loesch, D.Z., Godler, D.E., Khaniani, M., Gould, E., Gehling, F., Dissanayake, C., Burgess, T., Tassone, F., Huggins, R., Slater, H., et al. 2009. Linking the FMR1 alleles with small CGG expansions with neurodevelopmental disorders: preliminary data suggest an involvement of epigenetic mechanisms. Am J Med Genet A 149A:2306-10.

7.Loesch, D.Z., Khaniani, M.S., Slater, H.R., Rubio, J.P., Bui, Q.M., Kotschet, K., D'Souza, W., Venn, A., Kalitsis, P., Choo, A.K., et al. 2009. Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism. Clin Genet 76:471-6.

8.Godler, D.E., Tassone, F, Loesch, D.Z, Taylor, A.K, Gehling, F, Hagerman, R.J, Burgess, T,  Ganesamoorthy, D, Hennerich, D, Gordon, L, Evans, A, Choo, KHA, Slater, H. 2010. Methylation of novel markers of fragile X alleles is inversely correlated with FMRP and FMR1 activation ratio. Hum Mol Genet: 19, 1618-32.

9. Loesch, D.Z., Godler D.E., Evans, A., Bui M, Gehling, F., Kotschet, K.E., Trost, N., Storey, E.,

Stimpson, P.E., Kirk, J., Kinsella, G., Slater, H.R., Thorburn, D.R., Venn, A., Horne, M. 2011.

Evidence for the toxicity of bidirectional transcripts and mitochondrial dysfunction in blood

associated with small CGG expansions in the FMR1 gene in patients with parkinsonism.

Genet Med. 13(5):392-9.

10. Loesch, D.Z.,   Kotschet, K.E., Trost, N., Greco, C., Kinsella, G., Slater, H.R., Venn, A., Horne, M.

(2011). White matter changes in basis pontis in small expansion FMR1 allele carriers with

parkinsonism. Am J Med Genet B Neuropsychiatr  Genet 156 (4):502-6.

11. Godler, D.E., Slater, H.R., Bui, Q.M., Ono, M., Gehling, F., Francis, D., Amor, D.J., Hopper, J., Hennerich, D., Taylor, A.K., Hagerman, R., Loesch, D.Z. 2011.  FMR1 intron 1 methylation predicts FMRP expression in blood of female carriers of expanded FMR1 alleles. J Mol Diagn 13(5):528-36.

12. Loesch, D.Z., Hagerman, RJ. Unstable Mutations in the FMR1 Gene and the Phenotypes in: Tandem Repeat Polymorphisms: Genetic Plasticity, Neural Diversity and Disease (AJ Hannah, ed.). Landes Bioscience, Texas, USA, 2011.

13. Loesch, D.Z., Sherwell, S., Kinsella, G., Tassone, F., Taylor, A., Amor, D., Sung, S., Evans,

A. 2012.  Fragile X-associated tremor/ataxia phenotype in a male carrier of unmethylated full mutation in the

FMR1 gene. Clin Genet  82(1):88-92.

14. Godler, D.E., Slater, H.R., Bui, Q.M., Ono, M.Y., Gehling, F., Inaba, Y., Francis, D., Hopper, J.L., Kinsella, G., Amor, D., Hagerman, R.J., Loesch, D.Z. 2012. Fragile X mental retardation 1 (FMR1) intron 1 methylation in blood predicts verbal cognitive impairment in female carriers of expanded FMR1 alleles: evidence from a pilot study. Clin Chem 58(30):590-8.

15. Hamlin, A.A., Sukharev, D., Campos, L., Mu, Y., Hessl, D., Nguyen, D.V., Loesch, D.Z., Hagerman, R.J. 2012. Hypertension in FMR1 premutation males with and without fragile X-associated tremor/ataxia syndrome (FXTAS). Am J Med Genet A 158A(6):1304-9.

16. Hagerman, R.J.,Pak, J.S., Ortigas, M., Olichney O., Frysinger, R., Harrison, M., Cornman, E., Loesch, D.Z., Bittar, R.R., Peppard, R.,Zhang, L.,Shahlaie, K. 2012. Case Series: Deep Brain Stimulation in Patients with FXTAS. Brain Disorders and Therapy 1(2) 1000104 (open access).  

17. Inaba,Y., Herlihy, A.S., Schwartz, C.E., Skinner, C., Bui, Q.M.,  Cobb, J., Shi, E.Z., Francis, D.,  Arvaj, A.,  Amor, D.J.,  Pope,.K..,Wotton, T., Cohen,J.,  Hewitt,J.K.,  Hagerman, R.J., Metcalfe,S.A.,  Hopper,J.L.,  Loesch, D.Z., Slater, H.R.,  Godler, D.E. 2012.  Fragile X Related Element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study. Genet Med October 11. Doi:10.1038/gim 2012.134.[Epub ahead of print]..

18. Loesch, DZ., Slater H, Hills L, Bui M, Silburn P, Mellick G. 2012.  New evidence for, and challenges in, linking small CGG repeat expansion FMR1 alleles with Parkinson's disease. Clinic Genet  Nov 30, doi: 10.1111/cge.12070 [Epub ahead of print].

19. Godler, DE.,  Inaba, Y.,Shi, EZ,  Skinner, C., Bui, QM., Amor, DJ., Hopper, JL., Loesch, DZ., Hagerman , RJ., Schwartz, CE., Slater,HR. (2013). Relationships between age and epi-genotype of the FMR1 exon 1 / intron 1 boundary are consistent with non-random X-chromosome inactivation in FM individuals, with the selection for the unmethylated state being most significant between birth and puberty.  Hum Mol Genet January 18 [Epub ahead of print].

 

Older publications

Earlier publications (1984-2005) during  La Trobe period

 

63.   Loesch, D.Z. and Martin, N.G. (1984).  Finger ridge patterns and tactile sensitivity. Ann. Hum. Biol., 11 (2): 113.

64.   Loesch, D.Z. and Martin, N.G. (1984).  Relationships between minute characteristics of finger ridges and pattern size and shape.  Ann. Hum. Biol., 11(2): 125.

65.   Heath, A.C., Martin, N.G., Eaves, L.J. and Loesch, D.Z. (1984). Evidence for polygenic epistatic interactions in man?  Genetics, 106: 719.

66.   Loesch, D.Z. & Wolanski, N. (1985).  Dermal ridge patterns and fertility in a Polish rural sample.  Ann. Hum. Biol., 12(5): 463.

67.   Loesch, D.Z. & Hay, D.A. (1985).  Phenotypic diversity of fragile X females and its genetic implications (Abstract).  In Proceedings of Human Genetics Society of Australasia Meeting, Sydney, August 26th-30th, 1985, University of Sydney.

68.   Loesch, D.Z. & Hay, D.A. (1985).  What is fragile X?  La Trobe University.

69.   Loesch, D.Z. (1986).  Bivariate and multivariate analysis of the skin ridge pattern intensities.  Am. J. Phys. Anthrop., 69: 287.

70.   Loesch, D.Z. (1986).  Dermatoglyphic studies in the fragile X syndrome:  A causal hypothesis points to X-Y interchange,  Ann. Hum. Genet., 50(4): 385.

71.   Loesch, D.Z., Hay, D.A., Sutherland, G.R., Halliday, J., Judge, C., & Webb, G.C. (1987).  Phenotypic variation in male transmitted fragile X:  Genetic inferences.  Am. J. Med. Genet., 22(2): 401.

72.   Loesch, D.Z. (1987).  Factor analysis of ridge patterns and hand measurements in normal and fragile X males.  Coll. Anthrop. 11(2): 305.

73.   Loesch, D.Z. & Przybyla, B. (1988).  Dermatoglyphic variation and weight and length at birth.  Am. J. Phys. Anthrop., 75(1): 101.

74.   Loesch, D.Z. (1988).  Discriminant analysis of dermatoglyphic measurements in fragile X males and females.  Clin. Genet. 33: 169.

75.   Loesch, D.Z. & Hay, D.A. (1988).  Clinical features and reproductive patterns in fragile X female heterozygotes.  J. Med. Genet. 25: 407.

76.   Loesch, D.Z., Lafranchi, M., & Scott, D. (1988).  Anthropometry in Martin-Bell Syndrome.  Am. J. Med. Genet. 30: 149.

77.   Loesch, D.Z. & Wilson, S.R. (1989).  Multivariate analysis of body shape in fragile X (Martin-Bell) syndrome.  Am. J. Med. Genet. 33: 200.

78.   Wilson, S.R. & Loesch, D.Z. (1989).  Principal component analysis of shape variables in adult individuals.  Ann. Hum. Biol. 16(4): 361.

79.   Hay, D.A. & Loesch, D.Z. (1989).  Fragile X:  The new challenge in intellectual disability.  Psychobiology:  Issues and Applications.  N.S. Bond and D.A.T. Siddle (eds).  Elsevier Science Publishers B.V. (North Holland).

80.   Loesch, D.Z. & Scott, D. (1989).  Application of the anthropometric discriminant functions in estimation of carrier probabilities in Martin-Bell Syndrome.  Clin. Genet. 36: 145.

81.   Loesch, D.Z. & Lafranchi, M. (1990).  Relationships of epidermal ridge patterns with body measurements and their evolutionary significance.  Am. J. Phys. Anthrop. 82: 183.

82.   Loesch, D.Z., Lafranchi, M. & Ruffolo, C. (1990).  Hand locomotor functions, body structure, and epidermal ridge patterns: Preliminary study.  Hum. Biol. 62(5): 665.

83.   Loesch, D.Z., Lafranchi, M. & Huggins, R. (1991).  Application of anthropometric measurements in X-linked disorders, with special reference to fragile X syndrome.  J.Egypt Publ. Health Assoc. Vol 66 (Suppl): pp. 413-437.

84.   Loesch, D.Z., Hay, D.A. & Leversha, M. (1991).  Problems in ascertainment of transmitting males in Martin-Bell Syndrome. Am. J. Med. Genet. 41: 410.

85.   Loesch, D.Z. , Lafranchi, M. & Huggins, R. (1992).  New anthropometric scale for discrimination between sexes. Ann. Hum. Biol. 19(2): 177.

86.   Loesch, D.Z. & Huggins, R. (1992).  Fixed and random effects in the variation of the finger ridge count: A study of fragile X families.  Am. J. Hum. Genet. 50: 1067.

87.   Yu, S., Mulley, J., Loesch, D. & Turner, G. et al. (1992).  Fragile X syndrome: Unique genetics of the heritable unstable element. Am. J. Hum. Genet.  50: 968.

88.   Mulley, J.C., Yu, S., Gedeon, A.K., Donnelly, A., Turner, G., Loesch, D., Chapman, C.J. et al (1992).  Experience with direct molecular diagnosis of fragile X.  J. Med. Genet. 29: 368.

89.   Loesch, D.Z., Hay, D.A. & Sheffield, L. (1992).  Fragile X family with unusual digital and facial abnormalities, cleft lip and palate, and epilepsy. Amer. J. Med. Genet. 44: 543.

90.   Loesch, D.Z., Sheffield, L. & Hay, D.A. (1993).  Between generation differences in ascertainment and penetrance: relevance to genetic hypotheses in fragile X.  Hum. Genet. 91: 469.

91.   Loesch, D.Z., Huggins, R.M. & Chin, W.F. (1993).  Effect of fragile X on physical and intellectual traits estimated by pedigree analysis Am. J. Med. Genet. 46: 415.

92.   Loesch, D.Z. & Sampson, M. (1993). Effect of the fragile X anomaly on body proportions estimated by pedigree analysis. Clin. Genet. 44: 82.

93.   Loesch, D.Z., Huggins, R.M., Hay, D.A., Gedeon, A.K., Mulley, J.C., Sutherland, G.K. (1993).  Genotype-phenotype relationships in fragile X:  A family study. Am. J. Hum. Genet. 53(5): 1064.

94.   Loesch, D.Z. (1994). Epidermal ridge patterns in medicine. (Invited article.) Med. J. Aust. 161(11/12): 709.

95.   Loesch, D.Z., Hay, D.A. & Mulley, J. (1994). Transmitting males and carrier females in fragile X - revisited. Am. J. Med. Genet. 51: 392.

96.   Huggins, R.M. & Loesch, D.Z. (1994).  Applications of robust inference for variance components models:  the detection of major gene effects in finger ridge counts in normal and fragile X families. Aust. J. Stat. 36(3): 271.

97.   Mulley, J.C., Yu, S., Loesch, D.Z., Hay, D.A., Donnelly, A., Gedeon, A.K.,   Carbonell,P.,Lopez, I., Glover, G., Gabarron, I., Yu, P.W.L., Baker, E., Haan, E.A., Hockey, A., Knight, S.J.L., Davies, K.E., Richards, R.I. & Sutherland, G.R. (1995). FRAXE and mental retardation. J. Med. Genet. 32:162.

                        98.   Huggins, R.M. & Loesch, D.Z. (1995).  The use of robust statistical methods to determine the effect of fragile X on means and variance components of a quantitative trait. Genet. Epidemiol.12(3):279.

                        99. Loesch, D.Z., Hopper, J., Rogucka, E. & Huggins, R.M. (1995). Timing and genetic rapport between growth in skeletal maturity and height around puberty: similarities and differences between girls and boys Am. J. Hum. Genet. 56:753.

                        100. Loesch, D.Z., Huggins, R.M. & Hoang, N.H. (1995).  Growth in stature in fragile X families: a mixed longitudinal study. Am. J. Med. Genet. 58:249.

                        101. Loesch, D.Z., Huggins, R.M., Petrovic, V., Slater, H. (1995). Expansion of CGG repeat in fragile X depends on sex of the offspring: Genetic inferences. Am. J. Hum. Genet. 57:1408.

                          102.    Loesch, D.Z., Huggins, R.M., Rogucka, E., Hopper, J. & Hoang, N.G. (1995).  Genetic correlates of menarcheal age: A multivariate twin study. Ann. Hum. Biol. 22(6):479.

                        103. Loesch, D.Z. (1996). Fragile X-clinical associations (invited). Am. J. Med.Genet. 64 (2):413.

                        104. Loesch, D.Z., Petrovic, V., Francis, D.I. & Slater, H. (1997). Reduction of CGG trinucleotide expansion from mother to offspring in seven fragile X families. Clin. Genet. 51/1:1.

105. Loesch, D.Z. (1997). FMR1 fully expanded mutation with minimal methylation in a high functioning fragile X male. (Letter to the Editor). Brit. Med. J. 34 (4): 350.

                        106. Hill M, Nowson C, Huggins, RM, Tavener M. & Loesch DZ (1997). Self reported lifestyles of Melbourne schoolchildren 1992-1995: Relationship with physique. Austr J Nutr Diet 54:118.

107.   Loesch DZ & Huggins RM (1998) Mixed longitudinal study of Victorian schoolchildren.

 La Trobe University Press.

108. Huggins RM, Loesch DZ & Hoang NH (1998). A comparison of methods of fitting models to twin  data. Aust  NZ  J Stat  40(2):129.

109. Huggins RM & Loesch DZ (1998). On the analysis of mixed longitudinal growth data. Biometrics  54:583.

110. Loesch DZ, Huggins RM & Stokes KM (1999). The relationship of birth weight and                            length with growth in length and body diameters from 5 years of age to maturity.                                       Am J  Hum Biol 11:772. 

111. Cohen J & Loesch DZ (1999). Fragile X syndrome-what do professionals know about it?                    Med J Austr  190:624.

112. Loesch DZ, Stokes, K & Huggins RM (2000). Secular trend in body height and weight of                   Australian children and adolescents. Am J Phys Anthrop 111:545.

113. Tassone F, Hagerman RJ, Loesch DZ, Lachiewicz A, Taylor AK & Hagerman PJ (2000).                    Fragile X males with unmethylated full mutation trinucleotide repeat expansions  have  elevated              levels of FMR1 messenger RNA. Am J Med Genet 94(3):232.

114. Gould EL, Loesch DZ, Martin MJ, Hagerman RJ, Armstrong SM & Huggins RM (2000).                   Melatonin profiles and sleep characteristics in boys with fragile X syndrome: A                                         preliminary study. Am J Med Genet 95:307.

115. Huggins RM, Hoang NH & Loesch DZ (2000). On the analysis of longitudinal data from                    twins. Genetic Epidemiol 19:345.

116. Huggins RM, Qian G & Loesch DZ (2001). Inference on random coefficient models for                      haplotype effects in dynamic mutations using MCMC. Proceedings of the                                                 Symposium on Inference for Stochastic Processes (Eds: IV Basawa, CC Heyde & RL Taylor).                 Springer Verlag, New York, pp.185-202.

117. Loesch DZ, Huggins RM & Bui MM (2002). Application of robust pedigree analysis in studies of complex genotype-phenotype relationships in fragile X syndrome. Am J Med Genet 107:136.

118. Loesch DZ, Huggins RM, Bui MM, Taylor AK & Hagerman RJ (2002). Effect of the deficits of FMRP  on cognitive status of fragile X males and females assessed by robust pedigree analysis.  Dev Behav Pediat  23(6) : 416.

119. Loesch DZ, Huggins RM, Bui QM, Taylor AK, Hagerman RJ (2003). Relationship of deficits of FMR1 gene specific protein with physical phenotype of fragile X males and females in pedigrees: A new perspective. Am J Med Genet 118A(2):115.

120. Loesch DZ, Bui QM, Grigsby J, Butler E, Epstein J, Huggins RM, Taylor AK, Hagerman RJ (2003). Effect of the fragile X status categories and the FMRP levels on executive functioning in fragile X males and females.  Neuropsychology  17(4):646.

121. Loesch DZ, Huggins RM, Butler E, Taylor A, Hagerman RJ (2003). Effect of the fragile X status categories on cognitive profiles of fragile X males and females assessed by robust pedigree analysis.  Am J  Med Genet 23(6):416.

122. Saha S, Loesch DZ, Chant D, Welham J, El-Saadi O, Fananas L, Mowry B, McGrath J (2003). Directional and fluctuating asymmetry in finger and a-b ridge counts in psychosis: a case-control study. BMC Psychiatry  3 (March 23) : 3.

123. Loesch DZ, Huggins RM, Hagerman RJ (2004). Phenotypic variation and FMRP levels in fragile X. Ment Retard Dev Disabil Res Rev 10(1):31-41.

124. Huggins RM, Loesch DZ, Qian GQ, Bui QM, Mitchell RJ, Dobson M, Taylor AK (2004). Hierarchical Bayes model for random haplotype and family effects in the transmission of fragile X.  Genet Epidemiol, 26(4):294-304.

125. Huggins RM, Loesch DZ (2004). Robust nonparametric estimation of genotype-phenotype relationships in human pedigrees.  Aust  N Z J Stat 46(4):601-613.

126. Qian G, Huggins RM, Loesch DZ (2004). Application of the Rasch model in 16. Huggins RM, Loesch DZ, Qian GQ, Bui QM, Mitchell RJ, Dobson M, Taylor categorical pedigree analysis using MCEM: I Binary data. Discussiones Mathematicae, Probability and Statistics 24:255-280.

127. Mitchell RJ, Holden JA, Cuiling Z, Curlis Y, Slater HR, Burgess T, Kirkby KC, Carmichael A, Heading KD, Loesch DZ (2004). FMR1 (fragile X) alleles in Tasmania: a screening study of the special educational needs (SEN) population. Clin Genet 67:38-46.

128. Curlis Y, Cuiling Z,  Holden JA,  Kirkby K,  Loesch DZ,  Mitchell J (2005). Haplotype study of intermediate-length alleles at the fragile X (FMRI) gene: ATL1, FMRb, and microsatellite haplotypes differ from those found in common-size FMRI alleles. Hum Biol 77:137-151.

129. Loesch DZ, Churchyard A, Brotchie P, Marot M, Tassone F. (2005). Evidence for, and aspectrum of, neurological involvement in fragile X premutation: FXTAS and beyond. Clin Genet 67: 412-417.

130. Bui QM, Huggins RM, Qian GQ, Loesch DZ (2005). Random effects models for the transmission of dynamic mutations. 2004 Proceedings of the American Statistical Association, Statistical Computing Section (CD-ROM), Alexandria, VA: American Statistical Association.

131. Loesch  DZ, Bui QM, Kelso W, Huggins RM, Slater H, Warne G, Bergman P, Rodda C, Mitchell RJ, Prior M. (2005). Effect of Turner’s syndrome and X-linked imprinting on cognitive status: analysis based on pedigree data. Brain Dev 27(7):494-503.

132. Loesch DZ, Litewka L, Brotchie P, Huggins RM, Tassone F, Cook M. (2005). A MRI volumetric study in older carriers of a premutation in the FMR1 gene. Ann Neurol  58(2):326-330.

133. Hessl D, Tassone F, Loesch DZ, Berry-Kravis E, Leehey MA, Gane LW, Barbato I, Rice C, Gould E, Grigsby J,  Wegelin J, Harris S, Lewin F, Weinberg D, Hagerman P, Hagerman RJ. (2005). Abnormal elevation of FMR1mRNA is associated with psychopathology in adults with the fragile X premutation. Neuropsychiatr Genet. 139B(1):115-121.

 

 

Research projects

(1)  Genotype-phenotype relationships in fragile X families. This study investigates the influence of FMR1 gene variations in the phenotype of fragile X syndrome and premutation and ‘grey zone ‘carriers in addition to the influence of background gene effects by evaluating  available members of fragile X families using cognitive, behavioural, and physical measures, and relate these measure to the molecular changes. Supported by  NIH research grant No.5RO1 (HD36071) Hagerman / Loesch (PI/co-PI)    05/01/2012-04/30/2017. Dr Loesch is Principal Investigator for Australia

(2) The role of grey zone FMR1 alleles and related mitochondrial dysfunction in parkinsonian disorders.  This study addresses the clinical relevance of common (~1 in 120) grey zone (GZ) CGG expansions in the FMR1 gene. The FMR1 transcripts are elevated in GZ carriers, and mitochondrial dysfunction is involved in these transcripts’ neurotoxicity. Our earlier results also showed that GZ alleles are significantly more common in those with parkinsonism (PDS) than in the general population. This study aims to confirm the role of GZ alleles in the genesis, severity, and phenotypic features of PDS in a large clinical sample, and to explore the relationship of the elevated mRNAs to cellular stress, apoptosis and mitochondrial dysfunction. New application for  2013-2015  NHMRC project grant.