TY - JOUR
T1 - Hypermobile Ehlers-Danlos syndrome (hEDS) phenotype in fragile X premutation carriers
T2 - Case series
AU - Tassanakijpanich, Nattaporn
AU - McKenzie, Forrest
AU - McLennan, Yingratana A.
AU - Makhoul, Elisabeth
AU - Tassone, Flora
AU - Jasoliya, Mittal J.
AU - Romney, Christopher
AU - Petrasic, Ignacio Cortina
AU - Napalinga, Kaye
AU - Buchanan, Caroline B.
AU - Hagerman, Paul
AU - Hagerman, Randi
AU - Casanova, Emily L.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2021
Y1 - 2021
N2 - Background: While an association between full mutation CGG-repeat expansions of the Fragile X Mental Retardation 1 (FMR1) gene and connective tissue problems are clearly described, problems in fragile X premutation carriers (fXPCs) CGG-repeat range (55-200 repeats) of the FMR1 gene may be overlooked. Objective: To report five FMR1 fXPCs cases with the hypermobile Ehlers-Danlos syndrome (hEDS) phenotype. Methods: We collected medical histories and FMR1 molecular measures from five cases who presented with joint hypermobility and loose connective tissue and met inclusion criteria for hEDS. Results: Five cases were female and ranged between 16 and 49 years. The range of CGG-repeat allele sizes ranged from 66 to 150 repeats. All had symptoms of hEDS since early childhood. Commonalities in molecular pathogenesis and coexisting conditions between the fXPCs and hEDS are also presented. The premutation can lead to a reduction of fragile X mental retardation protein, which is crucial in maintaining functions of the extracellular matrix-related proteins, particularly matrix metallopeptidase 9 and elastin. Moreover, elevated FMR1 messenger RNA causes sequestration of proteins, which results in RNA toxicity. Conclusion: Both hEDS phenotype and premutation involvement may co-occur because of related commonalities in pathogenesis.
AB - Background: While an association between full mutation CGG-repeat expansions of the Fragile X Mental Retardation 1 (FMR1) gene and connective tissue problems are clearly described, problems in fragile X premutation carriers (fXPCs) CGG-repeat range (55-200 repeats) of the FMR1 gene may be overlooked. Objective: To report five FMR1 fXPCs cases with the hypermobile Ehlers-Danlos syndrome (hEDS) phenotype. Methods: We collected medical histories and FMR1 molecular measures from five cases who presented with joint hypermobility and loose connective tissue and met inclusion criteria for hEDS. Results: Five cases were female and ranged between 16 and 49 years. The range of CGG-repeat allele sizes ranged from 66 to 150 repeats. All had symptoms of hEDS since early childhood. Commonalities in molecular pathogenesis and coexisting conditions between the fXPCs and hEDS are also presented. The premutation can lead to a reduction of fragile X mental retardation protein, which is crucial in maintaining functions of the extracellular matrix-related proteins, particularly matrix metallopeptidase 9 and elastin. Moreover, elevated FMR1 messenger RNA causes sequestration of proteins, which results in RNA toxicity. Conclusion: Both hEDS phenotype and premutation involvement may co-occur because of related commonalities in pathogenesis.
KW - gene expression
KW - genetic predisposition to disease
KW - genetics
KW - human genetics
KW - medical
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U2 - 10.1136/jmedgenet-2020-107609
DO - 10.1136/jmedgenet-2020-107609
M3 - Article
AN - SCOPUS:85109032119
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
ER -