Hypermobile Ehlers-Danlos syndrome (hEDS) phenotype in fragile X premutation carriers: case series

While an association between full mutation CGG-repeat expansions of the ( ) gene and connective tissue problems are clearly described, problems in fragile X premutation carriers (fXPCs) CGG-repeat range (55-200 repeats) of the gene may be overlooked. To report five fXPCs cases with the hypermobile E...

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Bibliographic Details
Published in:	Journal of medical genetics Vol. 59; no. 7; p. 687
Main Authors:	Tassanakijpanich, Nattaporn, McKenzie, Forrest J, McLennan, Yingratana A, Makhoul, Elisabeth, Tassone, Flora, Jasoliya, Mittal J, Romney, Christopher, Petrasic, Ignacio Cortina, Napalinga, Kaye, Buchanan, Caroline B, Hagerman, Paul, Hagerman, Randi, Casanova, Emily L
Format:	Journal Article
Language:	English
Published:	England 01-07-2022
Subjects:	Child, Preschool Ehlers-Danlos Syndrome - complications Ehlers-Danlos Syndrome - diagnosis Ehlers-Danlos Syndrome - genetics Female Fragile X Mental Retardation Protein - genetics Fragile X Syndrome - complications Fragile X Syndrome - genetics Fragile X Syndrome - pathology Heterozygote Humans Male Phenotype Trinucleotide Repeat Expansion - genetics human genetics medical genetics genetic predisposition to disease gene expression
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Summary:	While an association between full mutation CGG-repeat expansions of the ( ) gene and connective tissue problems are clearly described, problems in fragile X premutation carriers (fXPCs) CGG-repeat range (55-200 repeats) of the gene may be overlooked. To report five fXPCs cases with the hypermobile Ehlers-Danlos syndrome (hEDS) phenotype. We collected medical histories and molecular measures from five cases who presented with joint hypermobility and loose connective tissue and met inclusion criteria for hEDS. 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 messenger RNA causes sequestration of proteins, which results in RNA toxicity. Both hEDS phenotype and premutation involvement may co-occur because of related commonalities in pathogenesis.
ISSN:	1468-6244
DOI:	10.1136/jmedgenet-2020-107609