Development of Genetic Testing for Fragile X Syndrome and Associated Disorders, and Estimates of the Prevalence of FMR1 Expansion Mutations

Macpherson, James

doi:10.3390/genes7120110

Cited by 12 publications

(11 citation statements)

References 53 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Majority of POF cases are idiopathic, while 10% are acquired due to chemotherapy, autoimmunity, or toxicity, and 20% have known genetic causes (Rossetti et al, 2016). Fragile X mutation or pre-mutation carriers comprise a bulk of individuals with known genetic causes of POF (Macpherson and Murray, 2016). The rest have mutations in autosomal genes, such as FOXL2, FSH receptor, aromatase and others, which were associated with POF (Laven, 2016).…”

Section: Physiology and Pathophysiology Of Lh And Fshmentioning

confidence: 99%

Regulation of reproduction via tight control of gonadotropin hormone levels

Coss

2018

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Mammalian reproduction is controlled by the hypothalamic-pituitary-gonadal axis. GnRH from the hypothalamus regulates synthesis and secretion of gonadotropins, LH and FSH, which then control steroidogenesis and gametogenesis. In females, serum LH and FSH levels exhibit rhythmic changes throughout the menstrual or estrous cycle that are correlated with pulse frequency of GnRH. Lack of gonadotropins leads to infertility or amenorrhea. Dysfunctions in the tightly controlled ratio due to levels slightly outside the normal range occur in a larger number of women and are correlated with polycystic ovaries and premature ovarian failure. Since the etiology of these disorders is largely unknown, studies in cell and mouse models may provide novel candidates for investigations in human population. Hence, understanding the mechanisms whereby GnRH regulates gonadotropin hormone levels will provide insight into the physiology and pathophysiology of the reproductive system. This review discusses recent advances in our understanding of GnRH regulation of gonadotropin synthesis.

show abstract

Section: Physiology and Pathophysiology Of Lh And Fshmentioning

confidence: 99%

Regulation of reproduction via tight control of gonadotropin hormone levels

Coss

2018

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

show abstract

“…In typical alleles, the fmr1 gene contains 5–54 CGG repeats (most commonly 30 repeats) while the pre-mutation alleles range from 55 to 200 CGG repeats. Additionally, pre-mutation fmr1 alleles are unstable and can become fully mutated alleles via maternal transmission [ 54 , 55 ].…”

Section: Fragile X Syndrome (Fxs)mentioning

confidence: 99%

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

Won

Jin

Choi

et al. 2017

IJMS

View full text Add to dashboard Cite

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation (fmr) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.

show abstract

“…For an individual child, the degree of functional disability depends on a complex interplay of cognitive deficits, fine-and gross-motor skills, voluntary behavior, and emotional regulation (Hartman, Houwen, Scherder, & Visscher, 2010;Lee & Jeoung, 2016;Mehregan, Najmabadi, & Kahrizi, 2016). For example, boys with fragile X syndrome (FXS; MIM #300624, see Online Mendelian Inheritance in Man in Web resources), a well-characterized monogenic cause of ID (Macpherson & Murray, 2016), often display stereotyped repetitive behaviors, hyperactivity, and/ or decreased motor coordination (Hagerman, Hoem, & Hagerman, 2010;Hall, Lightbody, & Reiss, 2008;Oakes et al, 2016). Stereotyped repetitive behaviors meet one of the core diagnostic criteria for autism spectrum disorder (ASD) (American Psychiatric Association, 2013), which cooccurs in a substantial minority of children with FXS (Abbeduto, McDuffie, & Thurman, 2014;Wheeler et al, 2015).…”

Section: Introductionmentioning

confidence: 99%