A girl with fragile X premutation from sperm donation
ABSTRACT 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 , with CGG repeat length explaining approximately 4% of the variance of verbal IQ per linear regression . Case studies have shown mixed results as well, with low [60,61] and superior  IQ scores both observed in girls with the premutation. Myers and colleagues  examined 14 children (7 female) and found a trend towards lower performance IQ, a measure closely related to executive functioning. "
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.Journal of Neurodevelopmental Disorders 07/2014; 6(1):30. DOI:10.1186/1866-1955-6-30 · 3.71 Impact Factor
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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.JAMA The Journal of the American Medical Association 10/2009; 302(15):1681-4. DOI:10.1001/jama.2009.1507 · 30.39 Impact Factor
Chapter: The Pathology of FXTAS[Show abstract] [Hide abstract]
ABSTRACT: In 2002 a syndrome of tremor, ataxia, cognitive decline, and the presence of unique ubiquitin staining intranuclear inclusions in the brain was discovered in premutation males carrying an expansion of between 55 and 200 CGG trinucleotide repeats on the FMR1 gene. This clinical syndrome is now known as fragile X-associated tremor/ataxia (FXTAS) and has been found in both male and female carriers of the expanded premutation allele. The goal of this chapter is to summarize what is known about the anatomical pathology associated with the fragile X premutation and particularly in those individuals with FXTAS. Neuropathology in FXTAS was initially found in the central nervous system, but recent evidence has demonstrated pathological features, including intranuclear inclusions, in the peripheral nervous system, the enteric nervous system, and the neuroendocrine system. The precise cellular dysfunctions that underlie these pathologic features are currently under intense investigation with the goal of prevention and treatment of this devastating disorder.02/2010: pages 67-76;