Mosaicism in Fragile X syndrome: A family case series.

Fragile X syndrome (FXS) has a classic phenotype, however its expression can be variable among full mutation males. This is secondary to variable methylation mosaicisms and the number of CGG triplet repeats in the non-coding region of the Fragile X Mental Retardation 1 () gene, producing a variable expression of the Fragile X Mental Retardation Protein (FMRP). Here we report a family with several individuals affected by FXS: a boy with a hypermethylated mutation and a classic phenotype; a man with an gene mosaicism in the range of premutation (PM) and full mutation (FM), who has a mild phenotype due to which FXS was initially disregarded; and the cases of four women with a FM and mosaicism.

FMR1 locus isoforms: potential biomarker candidates in fragile X-associated tremor/ataxia syndrome (FXTAS).

Fragile X associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder that affects movement and cognition in male and female carriers of a premutation allele of 55-200 CGG repeats in the Fragile X mental retardation (FMR1) gene. It is currently unknown if and when an individual carrier of a premutation allele will develop FXTAS, as clinical assessment fails to identify carriers at risk before significant neurological symptoms are evident. The primary objective of this study was to investigate the alternative splicing landscape at the FMR1 locus in conjunction with brain measures in male individuals with a premutation allele enrolled in a very first longitudinal study, compared to age-matched healthy male controls, with the purpose of identifying biomarkers for early diagnosis, disease prediction and, a progression of FXTAS.

Molecular Biomarkers Predictive of Sertraline Treatment Response in Young Children With Autism Spectrum Disorder.

Sertraline is one among several selective serotonin reuptake inhibitors (SSRIs) that exhibited improvement of language development in Autism Spectrum Disorder (ASD); however, the molecular mechanism has not been elucidated. A double blind, randomized, 6-month, placebo-controlled, clinical trial of low-dose sertraline in children ages (3-6 years) with ASD was conducted at the UC Davis MIND Institute. It aimed at evaluating the efficacy and benefit with respect to early expressive language development and global clinical improvement.

Rapidly Progressing Neurocognitive Disorder in a Male with FXTAS and Alzheimer's Disease.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that usually begins in the early 60s and affects carriers of premutation expansion (55-200 CGG repeats) of the fragile X mental retardation 1 () gene. Additional disorders can co-occur with FXTAS including Alzheimer's disease (AD). Here we discuss a case report of a male with 67 CGG repeats in who had mild late-onset FXTAS symptoms followed by neurocognitive disorder symptoms consistent with AD.

The role of AGG interruptions in the FMR1 gene stability: A survey in ethnic groups with low and high rate of consanguinity.

Background: The prevalence and the role of AGG interruptions within the FMR1 gene in the normal population is unknown. In this study, we investigated the frequent of AGG loss, in one or two alleles within the normal population. The role of AGG in the FMR1 stability has been assessed by correlating AGG loss to the prevalence of premutation/full mutation in two ethnic groups differing in their consanguinity rate: high versus low consanguinity rate (HCR vs.

Assessment of Molecular Measures in Non-FXTAS Male Premutation Carriers.

Approximately 30-40% of male and 8-16% of female carriers of the Fragile X premutation will develop a neurodegenerative movement disorder characterized by intentional tremor, gait ataxia, autonomic dysfunction, cognitive decline, and Parkinsonism during their lifetime. At the molecular level, premutation carriers have increased expression levels of the and the antisense ( mRNAs. Both genes undergo alternative splicing giving rise to a number of different transcripts.

Genetic cluster of fragile X syndrome in a Colombian district.

Background: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2-0.

Size and methylation mosaicism in males with Fragile X syndrome.

Background: Size and methylation mosaicism are a common phenomenon in Fragile X syndrome (FXS). Here, the authors report a study on twelve fragile X males with atypical mosaicism, seven of whom presented with autism spectrum disorder.

Methods: A combination of Southern Blot and PCR analysis was used for CGG allele sizing and methylation.

Altered expression of the FMR1 splicing variants landscape in premutation carriers.

FMR1 premutation carriers (55-200 CGG repeats) are at risk for developing Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), an adult onset neurodegenerative disorder. Approximately 20% of female carriers will develop Fragile X-associated Primary Ovarian Insufficiency (FXPOI), in addition to a number of clinical problems affecting premutation carriers throughout their life span. Marked elevation in FMR1 mRNA levels have been observed with premutation alleles resulting in RNA toxicity, the leading molecular mechanism proposed for the FMR1 associated disorders observed in premutation carriers.

Twin pregnancy outcomes after increasing rate of vaginal twin delivery: retrospective cohort study in a Hong Kong regional obstetric unit.

Objective: To determine any change in adverse neonatal/maternal outcomes after increasing the rate of vaginal twin delivery by comparing vaginal twin delivery and caesarean delivery with our previous cohort study.

Methods: In a retrospective cohort study, all twins booked at a Hong Kong regional obstetrics unit were evaluated during a 3-year period from 1 April 2009 to 31 March 2012.

Results: Out of the 269 sets of twins who eventually delivered in our unit, 68 (25.

Clinical and molecular implications of mosaicism in FMR1 full mutations.

Expansions of more than 200 CGG repeats (full mutation) in the FMR1 gene give rise to fragile X syndrome (FXS) through a process that generally involves hypermethylation of the FMR1 promoter region and gene silencing, resulting in absence of expression of the encoded protein, FMRP. However, mosaicism with alleles differing in size and extent of methylation often exist within or between tissues of individuals with FXS. In the current work, CGG-repeat lengths and methylation status were assessed for eighteen individuals with FXS, including 13 mosaics, for which peripheral blood cells (PBMCs) and primary fibroblast cells were available.

Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allopregnanolone.

Premutation CGG repeat expansions (55-200 CGG repeats; preCGG) within the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome (FXTAS). Defects in neuronal morphology and migration have been described in a preCGG mouse model. Mouse preCGG hippocampal neurons (170 CGG repeats) grown in vitro develop abnormal networks of clustered burst (CB) firing, as assessed by multielectrode array recordings and clustered patterns of spontaneous Ca(2+) oscillations, neither typical of wild-type (WT) neurons.

Screening for the presence of FMR1 premutation alleles in women with parkinsonism.

Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive, late-onset neurodegenerative disease that affects older carriers of premutation (CGG) repeat expansions of the fragile X mental retardation 1 (FMR1) gene. Clinical features include intention tremor, gait ataxia, memory loss, peripheral neuropathy, autonomic dysfunction, and parkinsonism. The presence of parkinsonism in FXTAS raises the possibility that some individuals who have Parkinson disease are actually carriers of a premutation FMR1 allele.

Screen for excess FMR1 premutation alleles among males with parkinsonism.

Background: Individuals with fragile X-associated tremor/ataxia syndrome frequently have associated features of parkinsonism, often leading to an initial diagnosis of Parkinson disease or other parkinsonism spectrum disorders. Parkinson disease populations may thus include individuals who harbor premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene.

Objective: To screen DNA samples (male) from an Italian Parkinson disease clinic for an excess of premutation expansions of the FMR1 gene.

Primary health care theory to practice: experience of first-year nursing students in Hong Kong.

In the past, nursing education in Hong Kong has focused on acute illness care, and institutions providing nursing education have been slow to modify the illness-focused curriculum to a health-based curriculum. The nursing curriculum at the University of Hong Kong is unique in that it focuses on primary health care, and these concepts are introduced in both theory and practice in the first year of the baccalaureate program. In the second semester of the first year, students are required to develop and implement a primary health care project in a community setting.