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10-03-2013 | Genetics | Article

Migraine common in fragile X premutation carriers

Abstract

Free abstract

medwireNews: People who carry the fragile X mental retardation 1 gene (FMR1) premutation are at significantly increased risk for migraine compared with those without the mutation.

"We hypothesize that the increased prevalence of migraine headaches in FMR1 premutation carriers is likely related to the mitochondrial abnormalities that have recently been reported," write Randi Hagerman (University of California, Sacramento, USA) and colleagues in Clinical Genetics.

"Screening for migraine should be considered when evaluating FMR1 premutation carriers in the future," they suggest.

FMR1 premutation carriers, who have a CGG trinucleotide repeat that is longer than normal but not long enough to cause fragile X syndrome, are relatively common in the general population. They are known to experience physiologic symptoms such as fragile

X-associated tremor ataxia syndrome or primary ovarian insufficiency, as well as anxiety, depression, hypertension, sleep apnea, fibromyalgia, and hypothyroidism.

Recent studies have also shown lower gamma-aminobutyric acid (GABA) receptor levels in these individuals, a characteristic previously linked to migraines.

To investigate if FMR1 premutation carriers have increased risk for migraine, Hagerman and team recruited 315 carriers (203 women; 112 men) and 154 controls (83 women; 71 men) all of whom had a standardized medical history and physical examination carried out by a physician who confirmed the presence or absence of migraine headaches.

They found that the prevalence of migraine in female and male carriers was 54.2% and 26.8%, respectively, compared with 25.3% in female and 15.5% in male controls, a statistically significant difference.

"This pathogenesis may be related to the increased prevalence of depression, anxiety, fibromyalgia, hypertension, sleep apnea and other neurological problems in FMR1 premutation carriers," say the researchers.

However, "we hypothesize that RNA toxicity leading to sequestration and protein dysregulation and the subsequent influence on mitochondrial function leads to the increased prevalence of migraines in FMR1 premutation carriers."

By Helen Albert, Senior medwireNews Reporter

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