Flora Tassone, Ph.D.
Tassone, Flora, Ph.D., Research Biochemist, Department of Biochemistry and Molecular
Medicine; Investigator, UC Davis MIND Institute, University of California, Davis
Education
B.S., Biology, University of Rome, 1983
Med Genetic, Medical Genetics, University of Rome, 1988
Ph.D., Molecular Biology, Catholic University of Rome, 1975
Biography
Dr. Flora Tassone received her B.S. degree in biology from the University of Rome “La
Sapienza” and her Ph.D. from the University of Rome UCSC in 1992. She is a research
biochemist in the Department of Biochemistry and Molecular Medicine, and a MIND Institute
investigator at the University of California, Davis, School of Medicine. She is a molecular
geneticist with a specialty in transcriptional and translational regulation of the fragile X
(FMR1) gene. Dr. Tassone has made a number of important observations related to the
mechanism of gene expression of the FMR1 gene, especially regarding the effects of
premutation alleles on individuals the scientific community thought to be clinically unaffected.
Specifically, she investigated the clinical manifestations, protein and FMR1 mRNA expression
in individuals with fragile X syndrome and made the important discovery of gene dysregulation
(increased activity) among premutation carriers. This discovery provided a molecular basis for
the forms of clinical involvement among carriers, including fragile X- associated tremor ataxia
syndrome (FXTAS). She continues to work on the molecular basis and abnormal molecular
phenotype observed in individuals with FXTAS. Dr. Tassone is the director of the Molecular
Core of a Fragile X project and she is the PI on a pilot study on Newborn Screening in Fragile
X syndrome, funded by the NIH, the first of its kind in United States. Her laboratory provides
the molecular support to a number of projects at the MIND Institute, as well as at the University
of California, Davis. Her research also focuses on a number of other neurodevelopmental
disorders including Autism Spectrum Disorders and 22q11.2 deletion syndrome.
Dr. Tassone has extensive experience in medical genetics and clinical analysis. She has been
granted multiple fellowships and training opportunities, as well as research awards from NIH,
the National Fragile X Foundation, and UC Davis Health System for her outstanding
contributions to the field. Dr. Tassone is well known in the international Fragile X community;
her work has been presented internationally and she has published extensively on the molecular
aspect of both Fragile X and FXTAS and autism.
Publications
Hoeffer CA, Sanchez E, Hagerman RJ, Mu Y, Nguyen DV, Wong H, Whelan AM, Zukin RS,
Klann E, Tassone F. Altered mTOR signaling and enhanced CYFIP2 expression levels in
subjects with Fragile X syndrome. Genes Brain Behav. 2012 Jan 23. [DOI: 10.1111/j.1601183X.2012.00768.x.]
This study reports on the dysregulation of the mTOR cascade signaling in subjects with fragile
X syndrome.
Hall D, Tassone F, Klepitskaya O, Leehey M. Fragile X-Associated tremor ataxia syndrome
in FMR1 gray zone allele carriers. Mov Disord. Dec 2011; 26(14) [DOI: 10.1002/mds.24021]
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McLennan Y, Polussa J, Tassone F, Hagerman R, Overview of Fragile X Syndrome. Current
Genomics. May 2011;12(3): 216-24.
This paper describes tremor and ataxia, which have previously been observed only in the
premutation range, in individuals with an intermediate allele.
Tassone F, Hagerman R. The fragile x-associated tremor ataxia syndrome. Results Probl Cell
Differ. 2012; 54:337-57.
This is a review on FXTAS.
Chonchaiya W, Au J, Schneider A, Hessl D, Harris SW, Laird M, My Y, Tassone F.
Increased Prevalence of Seizures in Boys Who Were Probands with the FMR1 premutation
and Co-Morbid Autism Spectrum Disorder. Hum Genet. 2011 Oct 14. [DOI: 10.1007/s00439011-1106-6]
This study demonstrates a higher prevalence of seizure and ASD in children with the
premutation, particularly in those who were probands of the family compared with their
siblings without a premutation.
Winarni TI, Utari A, Mundhofir FE, Tong T, Durbin-Johnson B, Faradz SM, Tassone F.
Identification of Expanded Alleles of the FMR1 Gene Among High-Risk Population in
Indonesia by Using Blood Spot Screening. Genet Test Mol Biomarkers. 2011 Oct 11. [DOI:
10.1089/gtmb.2011.0089]
This is a study on high risk screening for Fragile X an determination of prevalence in the
Indonesia populations.
Hamlin A, Liu Y, Nguyen DV, Tassone F, Zhang L, Hagerman RJ. Sleep apnea in fragile X
premutation carriers with and without FXTAS. Am J Med Genet B Neuropsychiatr y. 2011
Sep 19.
This paper reports on a higher prevalence and risk of sleep apnea in patients with FXTAS.
Leehey MA, Legg W, Tassone F, Hagerman R. Fibromyalgia in fragile X mental retardation 1
gene premutation carriers. Rheumatology (Oxford). Dec 2011; 50(12)2233-6.
This paper reports on an association between premutation alleles and fibromyalgia in female
carriers.
Stöger R, Genereux DP, Hagerman RJ, Hagerman PJ, Tassone F, Laird CD. Testing the
FMR1 Promoter for Mosaicism in DNA Methylation among CpG Sites, Strands, and Cells in
FMR1-Expressing Males with Fragile X Syndrome. PLoS One. Aug 2011;6(8):e23648.
This paper suggests the presence of cryptic mosaicism in individual with a FMR1 full
mutation.
Yrigollen CM, Tassone F, Durbin-Johnson B, Tassone F. The role of AGG interruptions in
the transcription of FMR1 premutation alleles. PLoS One. 2011;6(7):e21728.
This paper demostrates the lack of association between the presence of the AGG interruption
and the transcriptional activity of the FMR1 gene and describes a novel method to determine
their number of localization.
Goodrich-Hunsaker NJ, Wong LM, McLennan Y, Tassone F, Harvey D, Rivera SM, Simon
TJ. Adult Female Fragile X Premutation Carriers Exhibit Age- and CGG Repeat LengthRelated Impairments on an Attentionally Based Enumeration Task. Front Hum Neurosci.
2011;5:63.
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This study reports on the CGG repeat number and age dependency of cognitive impairment in
female carriers.
Selmeczy D, Koldewyn K, Wang JM, Lee A, Harvey D, Hessl DR, Tassone F, Adams P,
Hagerman RJ, Hagerman PJ, Rivera SM. Investigation of amygdala volume in men with the
fragile X premutation. Brain Imaging Behav. 2011 Dec;5(4):285-94
This study report on the negative effects of the presence of a premutation allele in the
amygdala.
Hunsaker MR, Greco CM, Spath MA, Smits AP, Navarro CS, Tassone F, Kros JM,
Severijnen LA, Berry-Kravis EM, Berman RF, Hagerman PJ, Willemsen R, Hagerman RJ,
Hukema RK. Widespread non-central nervous system organ pathology in fragile X
premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in
mice. Acta Neuropathol. 2011 Oct;122(4):467-79.
This study demonstrates for the first the presence of intranuclear inclusions in non CNS
organs and establish a parallel analysis between human and the premutation mouse model.
Hessl D, Wang JM, Schneider A, Koldewyn K, Le L, Iwahashi C, Cheung K, Tassone F,
Hagerman PJ, Rivera SM. Decreased Fragile X Mental Retardation Protein Expression
Underlies Amygdala Dysfunction in Carriers of the Fragile X Premutation. Biol Psychiatry.
2011 Nov 1;70(9):859-65.
This paper shows the role of reduced FMRP in alterations of brain activity and behavior in
premutation carriers.
Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F,
Hertz-Picciotto I. Prenatal Vitamins, One-carbon Metabolism Gene Variants, and Risk for
Autism. Epidemiology. 2011 Jul; 22(4):476-485.
This paper reports on the importance of the use of prenatal vitamin, in the context of a
genetic background of autism.
Hunsaker MR, Greco CM, Tassone F, Berman RF, Willemsen R, Hagerman RJ, Hagerman
PJ. Rare Intranuclear Inclusions in the Brains of 3 Older Adult Males With Fragile X
Syndrome: Implications for the Spectrum of Fragile X-Associated Disorders.. J Neuropathol
Exp Neurol. 2011 Jun;70(6):462-469.
This paper reports on the importance of the use of prenatal vitamin, in the context of a genetic
background to the risk of autism.
Hall DA, Berry-Kravis E, Zhang W, Tassone F, Spector E, Zerbe G, Hagerman PJ, Ouyang B,
Leehey MA. FMR1 gray-zone alleles: Association with Parkinson's disease in women? Mov
Disord. 2011 Aug 15;26(10):1900-6.
This study indicates a higher prevalence of gray zone alleles in females with parkinsonism.
Goodrich-Hunsaker NJ, Wong LM, McLennan Y, Tassone F, Harvey D, Rivera SM, Simon
TJ. Enhanced Manual and Oral Motor Reaction Time in Young Adult Female Fragile X
Premutation Carriers. J Int Neuropsychol Soc. 2011 Apr 21:1-5.
This study demonstrates that female carriers have enhanced basic psychomotor speed
relative to normal age matched controls.
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Tassone F, Qi L, Zhang W, Hansen RL, Pessah IN, Hertz-Picciotto I. MAOA, DBH, and
SLC6A4 variants in CHARGE: a case-control study of autism spectrum disorders. Autism
Res. 2011 Aug; 4(4):250-61.
This paper reports on the potential role of allelic variants in genes related to catecholamine
metabolism in autism.
Hashimoto RI, Srivastava S, Tassone F, Hagerman RJ, Rivera SM. Diffusion tensor
imaging in male premutation carriers of the fragile x mental retardation gene. Mov Disord.
2011 Jun; 26(7):1329-36.
This study provides new evidence from diffusion tensor imaging on the involvement of
molecular mechanisms related to the FMR1 gene in the white matter pathology observed
among individuals with the fragile X premutation.
Tassone F, De Rubeis S, Carosi C, La Fata G, Serpa G, Raske C, Willemsen R, Hagerman PJ,
Bagni C. Differential usage of transcriptional start sites and polyadenylation sites in FMR1
premutation alleles. Nucleic Acids Res. 2011 Aug; 39(14): 6172-85.
This papers reports on the structure of the 5’UTR and 3’UTR of the FMR1 genein both mouse
and human and suggests that the combination of alternative 5” and 3”UTRs increases
the complexity of FMR1 expression and the possible roles in FMR1 related disorders.
Loesch DZ, Sherwell S, Kinsella G, Tassone F, Taylor A, Amor D, Sung S, Evans A. Fragile
X-associated tremor/ataxia phenotype in a male carrier of unmethylated full mutation in the
FMR1 gene.Clin Genet. 2011 Apr 7. [DOI: 10.1111/j.1399-0004.2011.01675.x].
This paper reports the first FXTAS case of an individual with FXS.
Chen L, Hadd AG, Sah S, Houghton JF, Filipovic-Sadic S, Zhang W, Hagerman PJ, Tassone
F, Latham GJ. High-resolution methylation polymerase chain reaction for fragile X analysis:
Evidence for novel FMR1 methylation patterns undetected in Southern blot analyses. Genet
Med. 2011 Jun;13(6):528-38.
This study presents evidence of a methylation-sensitve PCR for the detection of methylated
alleles in subjects with FXS.
Hoem G, Raske CR, Garcia-Arocena D, Tassone F, Sanchez E, Ludwig AL, Iwahashi CK,
Kumar M, Yang JE, Hagerman PJ. CGG-repeat length threshold for FMR1 RNA pathogenesis
in a cellular model for FXTAS. Hum Mol Genet. 2011 Jun 1;20(11):2161-70.
This study shows the threshold CGG size effect on toxicity of FMR1 expanded alleles.
Hashimoto R, Javan AK, Tassone F, Hagerman RJ, Rivera SM. A voxel-based morphometry
study of grey matter loss in fragile X-associated tremor/ataxia syndrome. Brain. 2011
Mar;134(Pt 3):863-78.
This study reports on a gray matter loss in male premutation carriers with fragile x-associated
tremor/ataxia syndrome compared to the healthy controls.
Basuta K, Narcisa V, Chavez A, Kumar M, Gane WL, Hagerman JR, Tassone F. Clinical
phenotypes of a juvenile sibling pair carrying the fragile X premutation. American J of Med
Genet. 2011 Mar;155A(3):519-25
This is a case-report on the clinical outcomes in a compound heterozygous female and her
brother.
Greco CM, Navarro CS, Hunsaker MR, Maezawa I, Shuler JF, Tassone F, Delany M, Au JW,
Berman RF, Jin LW, Schumann C, Hagerman PJ, Hagerman RJ. Neuropathologic features in
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the hippocampus and cerebellum of three older men with fragile X syndrome. Mol Autism.
2011 Feb 8;2(1):2.
This paper reports on neurophatological significant findings in males with a full mutation,
which suggest defects in neuronal migration and/or neurogenesis.
Goodrich-Hunsaker NJ, Wong LM, McLennan Y, Srivastava S, Tassone F, Harvey D, Rivera
SM, Simon TJ. Brain Cogn. Young adult female fragile X premutation carriers show age- and
genetically-modulated cognitive impairments. 2011 Apr;75(3):255-60.
This paper demonstrates cognitive impairments in young adult female carriers that appear to
be age and CGG repeat number dependent.
Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F,
Pessah IN. Mitochondrial dysfunction in autism. JAMA. 2010 Dec 1;304(21):2389-96.
This study shows the presence of mitochondrial duysfunction in subjects with autism.
Schneider A, Ballinger E, Chavez A, Tassone F, Hagerman RJ, Hessl D. Prepulse inhibition
in patients with fragile X-associated tremor ataxia syndrome. Neurobiol Aging. 2010 Oct 18.
[DOI: 10.1016/j.neurobiolaging.2010.09.002]
The manuscript report of altered PPI in male premutation carriers.
Chonchaiya W, Tassone F, Ashwood P, Hessl D, Schneider A, Campos L, Nguyen DV,
Hagerman RJ. Autoimmune disease in mothers with the FMR1 premutation is associated with
seizures in their children with fragile X syndrome. Hum Genet. 2010 Nov; 128(5):539-48.
This study shows association between the presence immunodysfunction in female carriers of a
premutation and increased risk of seizure in their children.
Hall DA, Jennings D, Seibyl J, Tassone F, Marek K. FMR1 gene expansion and scans without
evidence of dopaminergic deficits in parkinsonism patients. Parkinsonism Relat Disord.
Parkinsonism Relat Disord. 2010 Nov;16(9):608-11.
This is a paper on clinical features in a patient carrier of the FMR1 premutation presenting
with parkinsonism.
Chen L, Hadd A, Sah S, Filipovic-Sadic S, Krosting J, Sekinger E, Pan R, Hagerman PJ,
Stenzel TT, Tassone F, Latham GJ. An Information-Rich CGG Repeat Primed PCR That
Detects the Full Range of Fragile X Expanded Alleles and Minimizes the Need for Southern
Blot Analysis. J Mol Diagn. 2010 Sep;12(5):589-600.
This paper reports on the validation of a novel PCR based approach capable of detecting
expanded alleles in all ranges in both genders.
Utari A, Adams E, Berry-Kravis E, Chavez A, Scaggs F, Ngotran L, Boyd A, Hessl D, Gane
LW, Tassone F, Tartaglia N, Leehey MA, Hagerman RJ. Aging in fragile X syndrome. J
Neurodev Disord. 2010 Jun;2(2):70-6.
This study reports on clinical problems in aging FXS subjects.
Hall D, Pickler L, Riley K, Tassone F, Hagerman R. Parkinsonism and cognitive decline in a
fragile X mosaic male. Mov Disord. 2010 Jul 30;25(10):1523-4.
This is a report on a size mosaic male presenting with symptoms and clinical features of
FXTAS.
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Hashimoto RI, Backer KC, Tassone F, Hagerman RJ, Rivera SM. An fMRI study of the
prefrontal activity during the performance of a working memory task in premutation carriers
of the fragile X mental retardation 1 gene with and without fragile X-associated tremor/ataxia
syndrome (FXTAS). J Psychiatr Res. 2011 Jan;45(1):36-43.
The results indicate altered prefrontal cortex activity likely related to executive and memory
defecits affecting some individuals with FMR1 premutation including FXTAS patients.
Yuhas J, Cordeiro L, Tassone F, Ballinger E, Schneider A, Long JM, Ornitz EM, Hessl D.
Brief Report: Sensorimotor Gating in Idiopathic Autism and Autism Associated with Fragile
X Syndrome. J Autism Dev Disord. 2011 Feb;41(2):248-53.
This study, using PPI, reports on differences in neurobiological processes in individuals with
FXS (with and without autism) and individuals with idiopathic autism.
Chonchaiya W, Nguyen DV, Au J, Campos L, Berry-Kravis EM, Lohse K, Mu Y, Utari A,
Hervey C, Wang L, Sorensen P, Cook K, Gane L, Tassone F, Hagerman RJ. Clinical
involvement in daughters of men with fragile X-associated tremor ataxia syndrome. Clin
Genet. 2010 Jul;78(1):38-46.
This manuscript shows an increased risk and presence of clinical involvement in females
carriers with a father with FXTAS.
Paul R, Pessah IN, Gane L, Ono M, Hagerman PJ, Brunberg JA, Tassone F, Bourgeois JA,
Adams PE, Nguyen DV, Hagerman R. Early onset of neurological symptoms in fragile X
premutation carriers exposed to neurotoxins. Neurotoxicology. 2010 Aug; 31(4):399-402.
This manuscript emphasizes the important role played by environmental insults in the onset
and severity of FXTAS.
Ottesen AM, Aksglaede L, Garn I, Tartaglia N, Tassone F, Gravholt CH, Bojesen A, Sørensen
K, Jørgensen N, Rajpert-De Meyts E, Gerdes T, Lind AM, Kjaergaard S, Juul A. Increased
number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with
sex chromosome aneuploidy. Am J Med Genet A. 2010 May;152A(5):1206-12.
This study reports on the association between gene copy number and stature in individuals
with sex chromosome aneuploidy.
Olichney JM, Chan S, Wong LM, Schneider A, Seritan A, Niese A, Yang JC, Laird K,
Teichholtz S, Khan S, Tassone F, Hagerman R. Abnormal N400 word repetition effects in
fragile X-associated tremor/ataxia syndrome. Brain. 2010 May; 133(Pt 5):1438-50.
This study reports on the effect of the presence of a premutation allele on the P600 and N400
word repetition effects in patients with FXTAS using an Event-related potential (ERP) word
repetition paradigm.
Sellier C., Rau F., Liu Y., Tassone F., Hukema R.K., Gattoni R., Schneider A., Richard S.,
Willemsen R., Elliott D.J., Hagerman P.J. & Charlet-Berguerand N. (2010) Partial Sam68
sequestration and partial loss of function are associated with splicing alterations in FXTAS
patients. EMBO J. Apr 7; 29 (7): 1248-1261.
This paper reports on the role of Sam68 in FXTAS. This protein is sequestered by expanded
CGG repeats and thereby loses its splicing-regulatory function. The consequence is altered
splicintg in FXTAS subjects.
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., Andy Choo K.H. & Robert Slater H.
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(2010) Methylation of novel markers of fragile X alleles is inversely correlated with FMRP
expression and FMR1 activation ratio. Hum Mol Genet. 2010 Apr 15; 19(8):1618-32.
This study reports on a correlation between methylation status and FMRP levels in subjects
with an FMR1 expanded allele.
Ashwood P., Nguyen D.V., Hessl D., Hagerman R.J. & Tassone F. (2010) Plasma cytokine
profiles in Fragile X subjects: Is there a role for cytokines in the pathogenesis? Brain Behav
Immun. Aug;24(6):898-902.
This paper demonstrated for the first time immune-dysregulation in subjects with Fragile X.
Filipovic-Sadic S., Sah S., Chen L., Krosting J., Sekinger E., Zhang W., Hagerman P.J.,
Stenzel T.T., Hadd A., Latham G.J. & Tassone F. (2010) A Novel FMR1 PCR Method for the
Routine Detection of Low-Abundance Expanded Alleles and Full Mutations in Fragile X
Syndrome. Clin Chem. Mar;56(3):399-408.
This paper describes the development of a novel PCR methodology capable of detected
expanded FMR1 alleles throughout all the mutation range.
Chonchaiya W., Utari A., Pereira G.M., Tassone F., Hessl D. & Hagerman R.J. (2009) Broad
clinical involvement in a family affected by the fragile X premutation. J Dev Behav Pediatr.
Dec; 30, 544-51.
This manuscript describes multiple clinical involvement in a family with gray zone and
premutation alleles.
Adams PE, Adams JS, Nguyen DV, Hessl D, Brunberg JA, Tassone F, Zhang W, Koldewyn
K, Rivera SM, Grigsby J, Zhang L, Decarli C, Hagerman PJ, Hagerman RJ. Psychological
symptoms correlate with reduced hippocampal volume in fragile X premutation carriers. Am J
Med Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):775-85.
This paper reports on the association between hippocampal volume and the severity of
anxiety-related psychological symptoms in female carreirs of a premutation allele.
Garcia-Arocena D, Yang JE, Brouwer JR, Tassone F, Iwahashi C, Berry-Kravis EM, Goetz
CG, Sumis AM, Zhou L, Nguyen DV, Campos L, Howell E, Ludwig A, Greco C, Willemsen
R, Hagerman RJ, Hagerman PJ. Fibroblast phenotype in male carriers of FMR1 premutation
alleles. Hum Mol Genet. 2010 Jan 15;19(2): 299-312.
This paper reports on cellular dysregulation in prmary fibroblast cell lines including
disruption of the lamin architecture and overexpression of stress response genes.
Chen Y, Tassone F, Berman RF, Hagerman PJ, Hagerman RJ, Willemsen R, Pessah IN.
Murine Hippocampal Neurons Expressing Fmr1 gene Premutations Show Early
Developmental Deficits and Late Degeneration. Hum Mol Genet. 2010 Jan 1;19(1):196-208.
This paper reports on early deficits in dendritic complexity, altered synaptic morphology and
decreased viability of mice premutation neurons.
Presentations
1) Prevalence and cascade testing for FMR1 mutation
2) Assessments of the AGG Structure in More than 1000 Samples Reveals the Risks of
Expansion for Intermediate and Low Premutation Fragile X Alleles.
3) Newborn screening in fragile X syndrome: a pilot study
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Poster presentations at the ACMG Annual Clinical Genetics Meeting, Vancouver, Canada,
March 2011
Alteration of the miRNA processing machinery and role of the ASFMR1 in FXTAS
Poster presentation, EMBO Meeting, Italy, August 2011
Update on a pilot study of newborn screening for Fragile X syndrome
Oral presentation at the 7th European Neonatal Screening Regional Meeting, Geneva, August
2011.
Molecular basis for a glutamatergic regulation in Fragile X Associated-Tremor Ataxia
Syndrome (FXTAS)
X-linked Disorders International Workshop, Berlin, Germany, September 2011.
Altered mTOR signaling in Fragile X syndrome
Oral presentation at the 2011 FRAXA Investigators Meeting, Southbridge, MA,
2011.
September
1) Newborn screening in fragile X syndrome
2) The molecular basis of fragile X and FMR1 associated disorders
Oral presentations, I Simposio Internacional dos Transtornos Associados a Sindrome do X
Fragile Florianopolis, Santa Caterina, Brazil, September 2011.
AGG interruptions: Risks of expansion to a full mutation
Oral presentation at the Society of Science for the Behavioral Phenotype, Brisbane,
Australia, October 2011.
1) The role of AGG interruptions in the FMR1 CGG repeats during transmission in a
clinical sample
2) Fragile X AGG genotyping reclassifies risk for expansion in intermediate and small
premutation carriers: Results of a multicenter study of 469 mother-child transmissions
3) Sequencing of expanded CGG repeats in the FMR1 gene
Poster presentations at the American Society of Human Genetics, Montreal, Canada,
October 2011.
Newborn screening project Update
Oral presentation at the Seattle Center Grant Retreat, Sacramento, California, October 2011.
Research Funding
Principal Investigator: Newborn Screening in Fragile X, NICHD, 7/1/08 — 6/30/13,
$473,494 annual direct. The overall objectives of the proposed research are to further refine
the rapid FMR1 DNA test, which is suitable for newborn screening from blood spots, and to
utilize this test for the purpose of obtaining initial estimates of the frequency and
approximate size distribution of expanded FMR1 alleles in the general population. This
project will also assess immediate and extended family members of the identified newborn
with the premutation of full mutation.
Investigator: Development of Targeted Therapeutic Agents for the Treatment of FXTAS,
NIA, 9/30/07 — 06/30/12, $578,879 annual direct. The principal objective of this project
will be the identification and assessment of various candidate therapeutic agents that might
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attenuate the effects of the pathogenic RNA in FXTAS. Research will also involve further
study of neural cell models of FXTAS.
Investigator: Expression of the Fragile X Gene, NICHD, 12/01/06 — 11/30/10, $212,500
annual direct.
This is a competing continuation of the original grant. In the proposed research, we propose
to identify the origin of altered expression of the FMR1 gene (low protein, fragile X
syndrome; elevate RNA, FXTAS) to facilitate the development of targeted approaches to
fragile X syndrome and FXTAS.
Investigator: Visual Processing and Later Cognitive Effects in Infants with Fragile X
Syndrome, NIH/NICHD, 06/01/07 — 05/31/12, $166,253 annual direct. This project is a
prospective, longitudinal study that will elucidate early visual processing differences in
infants with fragile X Syndrome and how abnormal visual processing, if present, relates to
cognitive deficits known to emerge in early childhood.
Investigator: Genotype-Phenotype Relationships in Fragile X Families, NICHD, 07/01/07–
06/30/12, $391,109. 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.
Investigator: Limbic System Function in Carriers of the Fragile X Premutation, NIMH,
07/01/07 — 06/30/12, $312, 072 annual direct. The present program of research will
investigate relations between molecular genetic, neuropsychological and physiological
systems underlying social-emotional and memory functioning in adult males with the fragile
X premutation (< 55 and < 200 CGG repeats), in comparison to their unaffected bioloogical
brothers and a group of men from the general population.
Investigator: Social-Affective Bases of Word Learning in Fragile X Syndrome and Autism,
NIH - subcontract (Randi Hagerman, UCD PI), 12/01/07 – 11/30/12, $279,298 annual
direct.
This project will provide important data for the development of language
interventions for FXS, as well as yielding insights into the causes and consequences of
variability in the FXS phenotype. Such data are particularly timely in light of recent
initiatives to conduct newborn screening for FXS, making the need for a wider range of
intervention options more urgent.
Principal Investigator: UC Davis Subcontract: Family Adapation to FXS: UC-Davis
Newborn Screening, NIH-subcontract, 4/1/08 – 3/31/13, $292,656 annual direct. This
project focuses on family adaptation to newborn screening for FXS. The study will provide
important information about the consequences of screening for both carriers and children
with the full mutation FXS and insight on]the extent to which families from diverse cultural
and ethnic groups consent to newborn screening for FXS, the reasons parents decline or
accept screening, and family or socio-cultural factors related to screening decisions.
Investigator: Treatment of Fragile X Syndrome with a Neuroactive Steroid
7/15/2011 – 7/14/2015, $972,780
This study is a Phase II trial to assess the safety, tolerability, and efficacy of ganaxolone, a
GABAA agonist, for the treatment of behavioral problems including anxiety and inattention
in children with FXS. Children who have the full mutation of fragile X between the ages of
6-17 years will be enrolled in this study.
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Investigator: Controlled Trial of Sertraline in Young Children with Fragile X Syndrome
9/1/2011 – 8/31/2014, $185,682 annual direct
This project evaluates the benefit of sertraline for treatment of early developmental delay,
including language delays, social deficits and attentional deficits, in young children with
FXS.
Community Service
Reviews for many Scientific Journals and Grant proposals
Awards and Honors
(2010) MIND Institute Research Award
(2009) 2009 Dean’s Team Award for Excellence
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