Overview

Fragile X syndrome (FXS) is the most common cause of inherited mental retardation with a worldwide prevalence of 1/4000 in males and of 1/8000 in females. Individuals with FXS exhibit a range of emotional and neurocognitive features including intellectual disability hyperactivity and attention problems, executive function deficits, hyperreactivity to stimuli, anxiety and mood instability, and ASDs. Fragile X syndrome is caused by a mutation int eh FMR1 gene leading to a deficit in FMR1 gene protein (FMRP). In general, the severity of the FXS physical phenotype and intellectual impairment is correlated with the magnitude of the FMRP deficit.

At this time, there is no specific treatment for FXS and clinical practice varies. The most common medications used to treat the FXS symptoms are stimulants (i.e. methylphenidate), selective serotonin reuptake inhibitors (SSRIs), alphaadrenoreceptor agonists, mood stabilizers, and antipsychotic medication. The use of any of these drugs is compromised by their limited efficacy and safety profile.

In recent years, there has been a new understanding of the neurobiology of FXS that involves the metabotropic glutamate receptor (mGluR). Based on the location and on the activity of mGluR in the central nervous system, there is a plausible relation between many of the phenotypic features in FXS and the deregulation of fragile X mental retardation protein (FMRP) activation. If this hypothesis is correct, mGluR antagonists should be a novel pharmacological approach to normalize the deficits caused by the lack of FMRP.

Publications

Rare SUZ12 variants commonly cause an overgrowth phenotype.
American journal of medical genetics. Part C, Seminars in medical genetics
Cyrus SS and Cohen ASA and Agbahovbe R and Avela K and Yeung KS and Chung BHY and Luk HM and Tkachenko N and Choufani S and Weksberg R and Lopez-Rangel E and C.A.U.S.E.S. Study and Gibson WT
DOI: 10.1002/ajmg.c.31748
PubMed: 31736240
11/2019

Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy.
Frontiers in neurology
Demos M and Guella I and DeGuzman C and McKenzie MB and Buerki SE and Evans DM and Toyota EB and Boelman C and Huh LL and Datta A and Michoulas A and Selby K and Bjornson BH and Horvath G and Farrer MJ
DOI: 10.3389/fneur.2019.00434
PubMed: 31164858
05/2019

NBEA: Developmental disease gene with early generalized epilepsy phenotypes.
Annals of neurology
Mulhern MS and Stumpel C and Stong N and Brunner HG and Bier L and Lippa N and Riviello J and Rouhl RPW and Kempers M and Pfundt R and Stegmann APA and Kukolich MK and Telegrafi A and Sands TT
DOI: 10.1002/ana.25350
PubMed: 30269351
10/2018

Genotype–phenotype analysis of 18q12.1-q12.2 copy number variation in autism
European Journal of Medical Genetics
Peter Wang and Prescilla Carrion and Ying Qiao and Christine Tyson and Monica Hrynchak and Kristina Calli and Elena Lopez-Rangel and Joris Andrieux and Bruno Delobel and Bénédicte Duban-Bedu and Ann-Charlotte Thuresson and Göran Annerén and Xudong Liu and Evica Rajcan-Separovic and M.E. Suzanne Lewis
DOI: 10.1016/j.ejmg.2013.05.006
08/2013

Clinical application of 2.7M Cytogenetics array for CNV detection in subjects with idiopathic autism and/or intellectual disability
Clinical Genetics
Qiao, Y. and Tyson, C. and Hrynchak, M. and Lopez-Rangel, E. and Hildebrand, J. and Martell, S. and Fawcett, C. and Kasmara, L. and Calli, K. and Harvard, C. and Liu, X. and Holden, J.J.A. and Lewis, S.M.E. and Rajcan-Separovic, E.
DOI: 10.1111/j.1399-0004.2012.01860.x
2013

The value of a genetic diagnosis for individuals with intellectual disabilities: Optimising healthcare and function across the lifespan
British Journal of Developmental Disabilities
Lopez-Rangel, E. and Mickelson, E.C.R. and Lewis, M.E.S.
DOI: 10.1179/096979508799103215
2008

The neoplastic risk in children with noonan syndrome and Costello syndrome
Clinical Genetics
Lopez-Rangel, E.
DOI: 10.1111/j.1399-0004.2006.00726_2.x
2007

Overlapping clinical phenotypes: The road to identifying dysmorphology signalling pathways and their associated risks
Clinical Genetics
Lopez-Rangel, E.
DOI: 10.1111/j.1399-0004.2006.00726_1.x
2007

Loud and clear evidence for gene silencing by epigenetic mechanisms in autism spectrum and related neurodevelopmental disorders.
Clinical genetics
Lopez-Rangel E and Lewis ME
DOI: 10.1111/j.1399-0004.2006.00543a.x
PubMed: 16451129
01/2006

Systemic lupus erythematosus and other autoimmune disorders in children with Noonan syndrome.
American journal of medical genetics. Part A
Lopez-Rangel E and Malleson PN and Lirenman DS and Roa B and Wiszniewska J and Lewis ME
DOI: 10.1002/ajmg.a.31017
PubMed: 16283670
12/2005

Prenatal exposure to fluconazole: an identifiable dysmorphic phenotype.
Birth defects research. Part A, Clinical and molecular teratology
Lopez-Rangel E and Van Allen MI
DOI: 10.1002/bdra.20189
PubMed: 16265639
11/2005

Molecular and clinical correlation study of Williams-Beuren syndrome: No evidence of molecular factors in the deletion region or imprinting affecting clinical outcome.
American journal of medical genetics
Wang MS and Schinzel A and Kotzot D and Balmer D and Casey R and Chodirker BN and Gyftodimou J and Petersen MB and Lopez-Rangel E and Robinson WP
DOI: 10.1002/(sici)1096-8628(19990903)86:13.0.co;2-4
PubMed: 10440826
09/1999

Molecular and clinical correlation study of Williams-Beuren syndrome: No evidence of molecular factors in the deletion region or imprinting affecting clinical outcome
American Journal of Medical Genetics
Wang, M.S. and Schinzel, A. and Kotzot, D. and Balmer, D. and Casey, R. and Chodirker, B.N. and Gyftodimou, J. and Petersen, M.B. and Lopez-Rangel, E. and Robinson, W.P.
DOI: 10.1002/(SICI)1096-8628(19990903)86:13.0.CO;2-4
1999

Bone dysplasias, nontraditional mechanisms of inheritance and monozygotic twins.
Pediatric radiology
Hall JG and Lopez-Rangel E
DOI: 10.1007/s002470050160
PubMed: 9133355
05/1997

An introduction to genomic imprinting and parent of origin effects.
Acta geneticae medicae et gemellologiae
Hall JG and Lopez-Rangel E
DOI: 10.1017/s0001566000001100
PubMed: 8872011
01/1996

Embryologic development and monozygotic twinning.
Acta geneticae medicae et gemellologiae
Hall JG and Lopez-Rangel E
DOI: 10.1017/s0001566000001094
PubMed: 8872010
01/1996

An introduction to genomic imprinting and parent of origin effects
Acta Geneticae Medicae et Gemellologiae
Hall, J.G. and Lopez-Rangel, E.
DOI: 10.1017/S0001566000001100
1996

Embryologic development and monozygotic twinning
Acta Geneticae Medicae et Gemellologiae
Hall, J.G. and Lopez-Rangel, E.
DOI: 10.1017/S0001566000001094
1996

New mechanisms for genetic disease and nontraditional modes of inheritance.
Advances in pediatrics
Langlois S and Lopez-Rangel E and Hall JG
PubMed: 8540441
01/1995

New mechanisms for genetic disease and nontraditional modes of inheritance.
Advances in pediatrics
Langlois, S. and Lopez-Rangel, E. and Hall, J.G.
1995

Non-traditional forms of inheritance in skeletal dysplasias.
Pediatric radiology
Hall JG and Lopez-Rangel E
DOI: 10.1007/bf02011905
PubMed: 7700715
01/1994

Non-traditional forms of inheritance in skeletal dysplasias
Pediatric Radiology
Hall, J.G. and Lopez-Rangel, E.
DOI: 10.1007/BF02011905
1994

Partial duplication of 3q (q25.1-->q26.1) without the Brachmann-de Lange phenotype.
American journal of medical genetics
Lopez-Rangel E and Dill FJ and Hrynchak MA and Van Allen MI
DOI: 10.1002/ajmg.1320470727
PubMed: 8291525
11/1993

Cardio-facio-cutaneous (CFC) syndrome in a child carrying an inherited inversion of chromosome 7.
American journal of medical genetics
Lopez-Rangel E and Hrynchak M and Friedman JM
DOI: 10.1002/ajmg.1320470306
PubMed: 8135275
09/1993

Williams syndrome in adults.
American journal of medical genetics
Lopez-Rangel E and Maurice M and McGillivray B and Friedman JM
DOI: 10.1002/ajmg.1320440605
PubMed: 1481839
12/1992

Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-onset Epilepsy
Michelle Demos and Ilaria Guella and Marna B. McKenzie and Sarah E. Buerki and Daniel M. Evans and Eric B. Toyota and Cyrus Boelman and Linda L. Huh and Anita Datta and Aspasia Michoulas and Kathryn Selby and Bruce H. Bjornson and Gabriella Horvath and Elena Lopez-Rangel and Clara DM van Karnebeek and Ramona Salvarinova and Erin Slade and Patrice Eydoux and Shelin Adam and Margot. I. Van Allen and Tanya N. Nelson and Corneliu Bolbocean and Mary B. Connolly and Matthew J. Farrer
DOI: 10.1101/139329

Research

Current Projects
Clinical Research Trials of mGluR antagonists for the treatment of Fragile X syndrome in pediatric and adult patients.

Honours & Awards

Scholarship to Study Abroad. Universidad Autonoma de Nuevo Leon, Nuevo Leon, Mexico Sept 1990 - Sept 1991

Summer Student Research Scholarship. Vancouver Foundation. Vancouver, British Columbia. 1991.

Effie E. Lefaux Scholarship in Mental Retardation. University of British Columbia. 1991.

Research Group Members

Maria Chan, Division Assistant, Sunnyhill