Intrasubject variability of sustained attention is associated with elevated self-reported attention deficits in women with a fragile X premutation allele.

Objective: Women with a fragile X premutation (PM) self-report higher rates of attention difficulties than women without a PM; however, results of studies using objective measures of attention are inconsistent. The present study assessed whether intrasubject variability during a sustained attention task better predicted functional outcomes in women with a PM than the previously published standard reaction time and accuracy variables.

Method: We analyzed continuous performance test, a computerized measure of sustained attention, and the Conners' Adult Attention-Deficit/Hyperactivity Disorder Rating Scale Report (CAARS) data from 273 women with a PM and 175 women without a PM aged 18-50 years.

Descriptive analysis of seizures and comorbidities associated with fragile X syndrome.

Background: Fragile X syndrome is characterized by a myriad of physical features, behavioral features, and medical problems. Commonly found behavioral features are hyperactivity, anxiety, socialization difficulties, and ASD. There is also a higher incidence than in the general population of strabismus, otitis media, and mitral valve prolapse.

Identification of as a genetic modifier of fragile X-associated tremor/ataxia syndrome.

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a debilitating late-onset neurodegenerative disease in premutation carriers of the expanded CGG repeat in FMR1 that presents with a spectrum of neurological manifestations, such as gait ataxia, intention tremor, and parkinsonism [P. J. Hagerman, R.

Predictors of Comorbid Conditions in Women Who Carry an Premutation.

Women who carry an premutation (PM) can experience two well-established PM-associated disorders: fragile X-associated primary ovarian insufficiency (FXPOI, affects ~20-30% carriers) and fragile X-associated tremor-ataxia syndrome (FXTAS, affects ~6-15% carriers); however, emerging evidence indicates that some of these women experience complex health profiles beyond FXPOI and FXTAS. In an effort to better understand predictors for these comorbid conditions, we collected self-reported medical histories on 413 women who carry an PM. There were 22 health conditions reported by at least 9% of women.

Identifying susceptibility genes for primary ovarian insufficiency on the high-risk genetic background of a fragile X premutation.

Objective: To identify modifying genes that explains the risk of fragile X-associated primary ovarian insufficiency (FXPOI).

Design: Gene-based, case/control association study, followed by a functional screen of highly ranked genes using a Drosophila model.

Setting: Participants were recruited from academic and clinical settings.

Refining the risk for fragile X-associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size.

Purpose: Approximately 20-30% of women with an FMR1 premutation experience fragile X-associated primary ovarian insufficiency (FXPOI); however, current risk estimates based on repeat size only identify women with the midrange of repeats to be at the highest risk.

Methods: To better understand the risk by repeat size, we collected self-reported reproductive histories on 1,668 women and divided them into high-resolution repeat size bins of ~5 CGG repeats to determine a more accurate risk for FXPOI in relation to CGG repeat length.

Results: As previously reported, women with 70-100 CGG repeats were at the highest risk for FXPOI using various statistical models to compare average age at menopause and risk of FXPOI, with women with 85-89 repeats being at the highest risk.

Men with an FMR1 premutation and their health education needs.

Men who carry an FMR1 premutation are at-risk to develop a late-onset neurodegenerative disorder called fragile X-Associated Ataxia/Tremor syndrome (FXTAS). However, little is known about their health informational needs. This qualitative study is the first to describe diagnostic experiences and identify specific health information needs of male premutation carriers.

Clustering of comorbid conditions among women who carry an FMR1 premutation.

Purpose: Emerging evidence indicates that women who carry an FMR1 premutation can experience complex health profiles beyond the two well-established premutation-associated disorders: fragile X-associated primary ovarian insufficiency (FXPOI, affects ~20-30% carriers) and fragile X-associated tremor-ataxia syndrome (FXTAS, affects ~6-15% carriers).

Methods: To better understand premutation-associated health profiles, we collected self-reported medical histories on 355 carrier women.

Results: Twenty-two health conditions were reported by at least 10% of women.

FXPOI: Pattern of AGG Interruptions Does not Show an Association With Age at Amenorrhea Among Women With a Premutation.

Fragile X-associated primary ovarian insufficiency (FXPOI) occurs in about 20% of women who carry a premutation allele (55-200 CGG repeats). These women develop hypergonadotropic hypogonadism and have secondary amenorrhea before age 40. A non-linear association with repeat size and risk for FXPOI has been seen in multiple studies women with a premutation: those with a mid-range of repeats are at highest risk (∼70-100 CGG repeats).

Olfactory dysfunction in fragile X tremor ataxia syndrome.

Introduction: We investigated olfactory defects in fragile X-associated tremor/ataxia syndrome (FXTAS), a finding reported on in other neurodegenerative disorders with clinical features that overlap those of FXTAS.

Methods: We measured olfactory identification capacity in 41 FMR1 premutation carriers and 42 controls using the University of Pennsylvania Smell Identification Test (UPSIT). Carriers received neurologic evaluations using motor rating scales for tremor, ataxia, and parkinsonism.

Depression and anxiety symptoms among women who carry the FMR1 premutation: impact of raising a child with fragile X syndrome is moderated by CRHR1 polymorphisms.

The fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat in the 5'-untranslated region of exon 1. Once unstable, this repeat is capable of expansion across generations. Women who carry a premutation allele (55-199 repeats) are at risk of passing on a full mutation allele (>200 repeats) to their offspring.

New clinical findings in the fragile X-associated tremor ataxia syndrome (FXTAS).

The objective of this paper was to assess the phenotypic variance in patients with the Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and to further elucidate genotype-phenotype correlations in the illness. A second goal was to generate hypotheses regarding symptom progression based on careful histories in our sample that can now be tested in ongoing longitudinal studies. The variability of clinical signs and symptom progression in FXTAS complicates our understanding of its phenotype and presents a series of problems in clinical trial design.

No evidence for a difference in neuropsychological profile among carriers and noncarriers of the FMR1 premutation in adults under the age of 50.

The 5' untranslated region of the fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat. Expansions of this repeat are associated with a spectrum of disorders. Full mutation alleles, repeats >or= 200, are associated with fragile X syndrome.

Investigation of phenotypes associated with mood and anxiety among male and female fragile X premutation carriers.

The fragile X disorder spectrum, due to a CGG expansion in FMR1, includes fragile X syndrome (>200 repeats) and the premutation-associated disorders of ovarian insufficiency and tremor/ataxia syndrome (approximately 55-199 repeats). Altered neurobehavioral profiles including variation of phenotypes associated with mood and anxiety may be expected among younger premutation carriers given this spectrum of disorders. However, previous studies have produced conflicting findings, providing the motivation to examine these phenotypes further.