The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study

• Published in: Journal of neurodevelopmental disorders Vol. 14; no. 1; p. 57
• Main Authors: Jalnapurkar, Isha, Frazier, Jean A, Roth, Mark, Cochran, David M, Foley, Ann, Merk, Taylor, Venuti, Lauren, Ronco, Lucienne, Raines, Shane, Cadavid, Diego
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.12.2022; BioMed Central; BMC
• Subjects: Autism; Clinical biomarker; Epigenetics; Feasibility studies; FMR1 mRNA; FMR1 protein; FMRP; Follicles; Fragile X; Fragile X Mental Retardation Protein - genetics; Fragile X syndrome; Fragile X Syndrome - genetics; Genetic aspects; Hair; Hair follicle; Hair Follicle - metabolism; Homeopathy; Humans; Intellectual disabilities; Male; Materia medica and therapeutics; Measurement; Medical research; Medicine, Experimental; Messenger RNA; mRNA; Mutation; Nervous system; Phenotypes; Pilot Projects; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sampling; Signal transduction; Synapses; Synaptic plasticity; Therapeutics; X chromosomes; Young adults; FMR1 mRNA; Hair follicle; Clinical biomarker; FMRP; Fragile X
• ISSN: 1866-1947; 1866-1955
• DOI: 10.1186/s11689-022-09465-7

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP. Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies.