Carriage of One or Two FMR1 Premutation Alleles Seems to Have No Effect on Illness Severity in a FXTAS Female with an Autozygous FMR1 Premutation Allele.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that occurs in FMR1 premutation carriers. The prevalence of FMR1 premutation carriers in the general population is relatively high, and although rare, a premutation in both X chromosomes may occur in females inheriting a premutation allele from each of both parent carriers. Here, we report the first female with an autozygous (homozygous by descendent) FMR1 premutation allele, who fulfills neurological and radiological FXTAS findings/criteria. Molecular characterization included CGG repeat length, AGG interruption pattern, FMR1 messenger RNA (mRNA), fragile X mental retardation protein (FMRP) level quantification, and single-nucleotide polymorphism (SNP) microarray. Neuroradiological assessment of 3-T magnetic resonance imaging and neurological and cognitive/neuropsychological evaluations were performed. Neurological and neuroradiological examination of the female with the same FMR1 allele in the premutation range (77 CGGs) demonstrated FXTAS features. Further familial evaluation showed a similar neuropsychiatric profile, with impairments in cognitive flexibility and visuospatial function, mainly. A unique family with an autozygous FMR1 premutation female is presented. Neurological/cognitive and neuroradiological examinations revealed FXTAS-specific findings in the female with the autozygous FMR1 premutation allele. The consistent molecular and cognitive/psychiatric phenotype in family members suggests that carrying one or two FMR1 premutation alleles has no effect on illness severity.
['Rodriguez-Revenga|Laia|L|', 'Pagonabarraga|Javier|J|', 'Gómez-Anson|Beatriz|B|', 'López-Mourelo|Olga|O|', 'Izquierdo|Silvia|S|', 'Alvarez-Mora|Maria Isabel|MI|', 'Granell|Esther|E|', 'Madrigal|Irene|I|', 'Milà|Montserrat|M|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000483:Alleles D001259:Ataxia D001921:Brain D005190:Family D005260:Female D051860:Fragile X Mental Retardation Protein D005600:Fragile X Syndrome D018628:Gene Dosage D006579:Heterozygote D006801:Humans D008297:Male D008875:Middle Aged D012720:Severity of Illness Index D014202:Tremor
FXTAS FMR1 premutation carrier FMR1 gene