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

Ramkumar Aishworiya; Mei-Hung Chi; Marwa Zafarullah; Guadalupe Mendoza; Matthew Dominic Ponzini; Kyoungmi Kim; Hazel Maridith Barlahan Biag; Angela John Thurman; Leonard Abbeduto; David Hessl; Jamie Leah Randol; Francois V Bolduc; Sebastien Jacquemont; Sarah Lippé; Paul Hagerman; Randi Hagerman; Andrea Schneider; Flora Tassone

doi:10.3390/cells12141920

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

Cells. 2023 Jul 24;12(14):1920. doi: 10.3390/cells12141920.

Authors

Ramkumar Aishworiya^{1

2

3}, Mei-Hung Chi^{1

4}, Marwa Zafarullah⁵, Guadalupe Mendoza⁵, Matthew Dominic Ponzini^{1

6}, Kyoungmi Kim^{1

6}, Hazel Maridith Barlahan Biag^{1

7}, Angela John Thurman^{1

8}, Leonard Abbeduto^{1

8}, David Hessl^{1

8}, Jamie Leah Randol^{5

9

10}, Francois V Bolduc¹¹, Sebastien Jacquemont^{12

13}, Sarah Lippé^{12

14}, Paul Hagerman^{1

5}, Randi Hagerman^{1

7}, Andrea Schneider^{1

7}, Flora Tassone^{1

5}

Affiliations

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.

Keywords: FMR1 mRNA; FMRP; MMP9; clinical trial; fragile X syndrome; outcome measures.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Fragile X Mental Retardation Protein / genetics
Fragile X Mental Retardation Protein / metabolism
Fragile X Syndrome* / diagnosis
Fragile X Syndrome* / genetics
Humans
Phenotype
RNA, Messenger / metabolism

Substances

Fragile X Mental Retardation Protein
Biomarkers
RNA, Messenger
FMR1 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding