Intercorrelation of Molecular Biomarkers and Clinical Phenotype Measures in Fragile X Syndrome

Author:

Aishworiya Ramkumar123ORCID,Chi Mei-Hung14,Zafarullah Marwa5ORCID,Mendoza Guadalupe5,Ponzini Matthew Dominic16,Kim Kyoungmi16,Biag Hazel Maridith Barlahan17,Thurman Angela John18,Abbeduto Leonard18ORCID,Hessl David18,Randol Jamie Leah5910,Bolduc Francois V.11,Jacquemont Sebastien1213,Lippé Sarah1214,Hagerman Paul15,Hagerman Randi17ORCID,Schneider Andrea17ORCID,Tassone Flora15

Affiliation:

1. MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA

2. Khoo Teck Puat-National University Children’s Medical Institute, National University Health System, Singapore 119074, Singapore

3. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore

4. Department of Psychiatry, National Cheng Kung University Hospital, Tainan 704, Taiwan

5. Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA

6. Department of Public Health Sciences, School of Medicine, University of California Davis, Sacramento, CA 95817, USA

7. Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, CA 95817, USA

8. Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California Davis, Sacramento, CA 95817, USA

9. Integrative Genetics and Genomics Graduate Group, University of California Davis, One Shields Avenue, Davis, CA 95616, USA

10. UC Davis Biotechnology Program, University of California Davis, Davis, CA 95616, USA

11. Department of Pediatrics, Department of Medical Genetics, Women and Children Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada

12. CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC H3T 1J4, Canada

13. Department of Pediatrics, University of Montreal, Montreal, QC H3T 1J4, Canada

14. Department of Psychology, Université de Montréal, Montreal, QC H3T 1J4, Canada

Abstract

This study contributes to a greater understanding of the utility of molecular biomarkers to identify clinical phenotypes of fragile X syndrome (FXS). Correlations of baseline clinical trial data (molecular measures—FMR1 mRNA, CYFIP1 mRNA, MMP9 and FMRP protein expression levels, nonverbal IQ, body mass index and weight, language level, NIH Toolbox, adaptive behavior rating, autism, and other mental health correlates) of 59 participants with FXS ages of 6–32 years are reported. FMR1 mRNA expression levels correlated positively with adaptive functioning levels, expressive language, and specific NIH Toolbox measures. The findings of a positive correlation of MMP-9 levels with obesity, CYFIP1 mRNA with mood and autistic symptoms, and FMR1 mRNA expression level with better cognitive, language, and adaptive functions indicate potential biomarkers for specific FXS phenotypes. These may be potential markers for future clinical trials for targeted treatments of FXS.

Funder

Azrieli Foundation

MIND Institute IDDRC

Publisher

MDPI AG

Subject

General Medicine

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