Flora Tassone, Ph.D.

Associate Research Biochemist, Department of Biochemistry and Molecular Medicine, School of Medicine

University of California, Davis
4206 Tupper Hall
Davis, CA 95616
E-mail:  ftassone@ucdavis.edu

Dr. Tassone is a molecular biologist with expertise in the regulation of gene expression. Her research focuses on understanding the genetic basis of fragile X syndrome and autism. During her short career, she has made fundamental contributions to fragile X research. For example, her discovery of gene dysregulation (increased activity) among premutation carriers provided a molecular explanation for the clinical involvement seen among carriers and to the recent identification of a new neurodegenerative disorder, Fragile X associated tremor/ataxia syndrome. This disorder affects older adult males with premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Recently, she has focused her efforts in autism research, and is currently evaluating the specific role of a number of genes and of their genetic variability in autism. She is the Molecular Core Director on a NIH/NICHHD-funded Program Project Grant.

Moore CJ, Daly EM, Schmitz N, Tassone F, Tysoe C, Hagerman RJ., Hagerman PJ., Morris RG Murphy K.C., Murphy DGM. A neuropsychological investigation of male premutation carriers of fragile X syndrome. Neuropsychologia 42(14):1934-47, 2004. FMR1 premutation can affect brain functions. Specifically, cognitive and neuropsychological deficits are observed in male carriers of the FNR1 premutation.

Zeesman S, Zwaigenbaum L, Whelan DT, Hagerman RJ, Tassone F, Taylor SAM. Paternal transmittion of Fragile X syndrome. Am J Med Gene 129 A(2):184-18, 2004. This paper is the first report of a paternally-derived full mutation expressed in a female.

Garcia Arocena, D, Louis ED, Tassone F, Gilliam TC, Ottman R, Jacquemont S,  Hagerman PJ. Screen for expanded FMR1 alleles in patients with essential tremor. Movement Disorders 19(8)930-933, 2004. This paper emphasizes the importance of screening patients affected by movement disorders for the presence of a fragile X premutation.

Hagerman RJ, Leavitt BR,  Farzin F, Jacquemont S, Greco C, Brunberg J, Tassone F,  Hessl D, Harris S,  Zhang L,  Jardini T, Gane L, FerrantiJ, Ruiz L, Leehey M, Hagerman PJ. Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) in Females with the FMR1 Premutation. Am J Hum Genet 74(5): 1051-1056, 2004. Reports study demonstrating that older females with the premutation may also develop FXTAS.

Jacquemont S, Farzin F, Hall DA, Leehey MA, Tassone F, Gane LW, Zhang L, Grigsby J, Jardini T, Lewin F, Berry-Kravis E, Hagerman PJ, Hagerman RJ.  Aging in individuals with the FMR1 mutation. Am J Ment Retard 109,2:154-164, 2004. Paper reports the aging and the neurological problems that occur in those with the fragile X mutation.

Beilina A, Tassone F, Schwartz PH, Sahota P, Hagerman, PJ. Redistribution of transcription start sites within the FMR1 promoter region with expansion of the downstream CGG-repeat element. Hum. Mol. Genet. 13,5:543-549, 2004. Transcription of the FMR1 gene is initiated from several transcription start sites and is modulated by the downstream CGG repeat.

Jacquemont S, Hagerman RJ, Leehey MA, Hall DA, Levine RA, Brunberg JA, Zhang L, Jardini T, Gane LW, Harris SW, Herman K, Grigsby J, Greco CM, Berry-Kravis E, Tassone F, Hagerman PJ. Penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) in a premutation carrier population: Initial results from a California family-based study.  JAMA 291:460-469, 2003. The fragile X premutation leads to a neurological syndrome (FXTAS) in at least 30% of older male carriers.

Chen L-S, Tassone F, Sahota P, Hagerman P J. The (CGG)n repeat element within the 5' untranslated region of the FMR1message provides both positive and negative cis effects on in vivo translation of a downstream reporter. Hum Mol Genet (12)23:3067-3074, 2003. The investigation demonstrated that the expression of the fragile X gene also is regulated at the level of translation in a manner that depends on the 5’ untranslated region of the FMR1 message. Specifically a translational activation is observed for smaller CGG repeat numbers. On the contrary, larger expansions cause inhibition of translation.

Tassone F, Hagerman RJ. Garcia Arocena D, Khandjian EW, Greco CM, Hagerman PJ. Intranuclear inclusions in fragile X-associated tremor/ataxia syndrome (FXTAS) neural cells with premutation alleles. Journal of Medical Genetics.41(4):e43. This work establishs a direct association between premutation alleles and inclusion formation, thus excluding the possibility that cryptic full mutation alleles are responsible for either inclusion formation or FXTAS.

Tassone F,  Hagerman P. Expression of the FMR1 gene. Cytogenetic and Genome Research. 100:124-128, 2003. A review of the factors governing the expression of the fragile X mental retardation 1 gene, the gene responsible for the leading heritable form of mental retardation.

Jacquemont S, Hagerman RJ, Leehey MA, Hall DA, Levine RA, Brunberg JA, Zhang Lin, Jardini T, Gane LW, Harris SW, Herman K, Grigsby J, Greco C, Berry-Kravis E, Tassone F, Hagerman PJ. Penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) in a premutation carrier population: Initial results from a California family-based study. JAMA 291(4): 460-469, 2004.  The fragile X permutation, which is associated with autism in some carriers, frequently leads to neurological problems in grandfathers.

Leehey MA, Munholz RP, Lang AE, Bruanberg JA, Grisby J, Greco C, Jacquemont S, Tassone F, Lozano AM,  Hagerman PJ, Hagerman RJ.  The Fragile X Premutation Presenting as Essential Tremor.  Arch Neurol 60: 117-212, 2003. This is a case report of two adult males who presented with essential tremor, but they really had FXTAS (Fragile X Tremor Ataxia Syndrome). The course of the syndrome, as well as problems associated with surgery in one of the cases is discussed.

Willemsen R, Hoogeveen-Westerveld M, Reis S, Holstege J, Severijnen LA, Nieuwenhuizen IM, Schrier M, Van Unen L, Tassone F, Hoogeveen A T, Hagerman PJ, Mientjes EJ, Oostra BA. The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. Hum Mol Genet 12(9), 949-59, 2003. The presence of neuronal intranuclear inclusion in mice carrying a CGG repeat expansion supports a direct role of the FMR1 gene, either by the presence of CGG element or by the mRNA level.

Intranuclear inclusions in Fragile X associated tremor/ataxia syndrome neural cells with permutation alleles,  11th International Meeting on Fragile X syndrome and X-linked mental retardation,  Cyprus, August 2003.

Molecular studies in fragile X-associated tremor/ataxia syndrome (FXTAS) neuronal cells from five premutation carriers,  American Society of Human Genetics Meeting, Los Angeles, CA, November 2003.

Fragile X neuroprogenitor cells, 9th International Fragile X Conference, Washington DC, June 2004.

Investigator (PI: PJ Hagerman):  Expression of the Fragile X Gene, NIH/NICHD, 4/02-3/06, $372,500 annual direct. The goal of this study is to examine the mechanisms underlying both the silencing of the FMR1 gene and the increase in FMR1 mRNA observed for carriers of premutation FMR1 alleles.

Investigator: Neurological Phenotype in FMR1 Premutation Carriers, NIH/NINDS, 7/02-6/06, $290,425 annual direct. This project represents a three-center consortium established to determine the relationship between premutation carrier status and a newly described neurological phenotype involving tremor, ataxia, and cognitive decline.

Investigator (PI: R Hagerman): Genotype-Phenotype Relationships in Fragile X Families, NIH/NICHHD, 6/98-5/06, $394,000 annual direct. This grant will correlate FMRP and other molecular measures with anthropometric, IQ and behavioral measures in families with FXS.  It will also investigate the features of premutation carriers of fragile X syndrome

Co-Investigator: Action Tremor and Dementia in Male Carriers of Fragile X, NIH/NICHHD, 09/03-06/08, $194,594 annually. This grant evaluates the adult male carriers of fragile X who have problems with tremor and dementia.

Investigator and Director of Molecular Core: Fragile X Research Center at UC Davis, NIH/NICHHD, 07/03-06/08, $215,136 annually. This is a component of a center grant in collaboration with the University of Washington Mental Retardation Research Center.