A girl with fragile X premutation from sperm donation

MIND Institute, University of California-Davis Medical Center, Sacramento, California 95817, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 04/2008; 146(7):888-92. DOI: 10.1002/ajmg.a.31876
Source: PubMed


We present a girl with the fragile X premutation who obtained the premutation allele from donated sperm. Our patient has clinical characteristics of fragile X syndrome including emotional problems and neuropsychological difficulties presenting as learning disabilities. She is also at high risk for premature ovarian failure and low risk for the fragile X-associated tremor ataxia (FXTAS). We suggest fragile X DNA screening in gamete donor candidates to decrease the chance of fragile X involvement in their offspring.

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    • "In contrast, a few reports have documented lower verbal IQ scores among these women compared to female normal controls [44,58] or their male counterparts [59], with CGG repeat length explaining approximately 4% of the variance of verbal IQ per linear regression [44]. Case studies have shown mixed results as well, with low [60,61] and superior [62] IQ scores both observed in girls with the premutation. Myers and colleagues [63] examined 14 children (7 female) and found a trend towards lower performance IQ, a measure closely related to executive functioning. "
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    ABSTRACT: Changes in the fragile X mental retardation 1 gene (FMR1) have been associated with specific phenotypes, most specifically those of fragile X syndrome (FXS), fragile X tremor/ataxia syndrome (FXTAS), and fragile X primary ovarian insufficiency (FXPOI). Evidence of increased risk for additional medical, psychiatric, and cognitive features and conditions is now known to exist for individuals with a premutation, although some features have been more thoroughly studied than others. This review highlights the literature on medical, reproductive, cognitive, and psychiatric features, primarily in females, that have been suggested to be associated with changes in the FMR1 gene. Based on this review, each feature is evaluated with regard to the strength of evidence of association with the premutation. Areas of need for additional focused research and possible intervention strategies are suggested.
    Full-text · Article · Jul 2014 · Journal of Neurodevelopmental Disorders
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    ABSTRACT: Sperm donation is an increasingly common practice for achieving pregnancy in the absence of a male partner or when fertility is problematic. The unintended consequence in which genetic diseases are unwittingly transmitted to offspring is an underrecognized public health issue not previously prioritized by US Food and Drug Administration guidelines. To report the clinical circumstances and implication of hypertrophic cardiomyopathy (HCM) transmitted by sperm donation to recipients. Voluntary sperm donation through a US Food and Drug Administration-approved tissue bank. Incidence of genetically affected offspring and clinical outcomes to date. An asymptomatic 23-year-old man who had no personal knowledge of underlying heart disease and who underwent standard testing that was negative for infectious diseases, repeatedly donated sperm over a 2-year period (1990-1991). The donor was later shown to be affected (in 2005) by a novel beta-myosin heavy-chain mutation that caused HCM, after an offspring was clinically diagnosed with this disease. Of the 24 children known to be offspring of the donor, including 22 who were products of fertilization via sperm donation and 2 conceived by the donor's wife, a total of 9 genetically affected offspring, 2 to 16 years of age and 6 males, have been identified with HCM (2005-2009). Three of the 9 gene-positive children have currently expressed phenotypic evidence of HCM, including one who died at age 2 years due to progressive and unrelenting heart failure with marked hypertrophy, and also 2 survivors with extreme left ventricular hypertrophy at age 15 years. The latter 2 children and the donor are judged likely to be at increased risk for sudden death. This case series underscores the potential risk for transmission of inherited cardiovascular diseases through voluntary sperm donation, a problem largely unappreciated by the medical community and agencies regulating tissue donation. Recommendations include improved screening guidelines for donors to exclude cardiovascular diseases (eg, HCM) such as consideration for 12-lead electrocardiograms.
    Preview · Article · Oct 2009 · JAMA The Journal of the American Medical Association
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    ABSTRACT: Data concerning the neuropsychological and neuropsychiatric phenotypes of the fragile X-associated tremor/ataxia syndrome (FXTAS) are providing an increasingly clear picture of the cognitive and behavioral features of this neurodegenerative disorder. This is true especially for males, among whom FXTAS has been reasonably well characterized. As FXTAS is a recently identified disorder, despite a considerable amount of research, many questions remain. For example, women, in part because of the presence of a normal allele on the second X chromosome, tend to have significant differences in penetrance and expression of FMR1 gene mutations; hence there are marked gender differences in the phenotype, and relatively little is known about the female phenotype. Moreover, the factors that account for severity and progression within a given individual are as yet unclear. This chapter addresses studies of the cognitive and emotional signs and symptoms of FXTAS, especially insofar as they are seen in males. We summarize what is known about cognition and psychiatric functioning in affected individuals and consider some of the many unknowns. For the most part, the neuropsychological deficits associated with FXTAS involve impaired executive cognitive functioning. Hence, one frequently observes disorders of behavioral self-regulation, planning, inhibition, working memory, and information processing. These deficits appear to interact with, and contribute to, psychiatric symptomatology such as anxiety, impulsivity, apathy, irritability, and agitation. Most studies to date have been cross-sectional, and it is not yet possible to draw inferences regarding the progression and timing of cognitive decline in FXTAS. Moreover, as some individuals with FXTAS have minimal or no cognitive/psychiatric impairment, even in the presence of significant neurological deficits, these manifestations of the disorder may be quite heterogeneous. Further research will enhance our understanding of this disorder, of the temporal and symptomatic relationships between neuropsychological and neurological findings, and of other genetic and epigenetic variables that determine the development, course, penetrance, and severity of FXTAS.
    Full-text · Chapter · Feb 2010
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