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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term "paternal age effect" (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time-explaining the observed paternal age effect associated with these disorders-and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition.
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PMID:Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. 2232 59

There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. The authors present a novel mechanism that may contribute to this association. Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation through dysregulation of the RAS protein pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare disorders related to paternal age (e.g., Apert syndrome, achondroplasia), this process is known as "selfish spermatogonial selection." This mechanism favors propagation of germ cells carrying pathogenic mutations, increasingly skews the mutational profile of sperm as men age, and enriches de novo mutations in the offspring of older fathers that preferentially affect specific cellular signaling pathways. This mechanism not only offers a parsimonious explanation for the association between advanced paternal age and various neurodevelopmental disorders but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle), and some epidemiological features of these disorders. The authors outline hypotheses to test this model. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public health implications.
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PMID:"Selfish spermatogonial selection": a novel mechanism for the association between advanced paternal age and neurodevelopmental disorders. 2363 89

This case focused on a 7-year-old boy with Apert and Asperger's syndrome who attended 8, 45 min multisensory yoga sessions, twice a week, during 4-week camp. Results from the pre- and post-tests on Treatment and Research Institute for Autism Social Skills Assessment showed improvements in the total score changes from 19 to 7 for disruptive behaviors. Sparks Target Behavior Checklist scores changed from eight to one showing progression in ability to stay on task. Yoga Pose Rating Scale displayed the transformation in total scores from 80 = emerging to 115 = consistency in pose performance. The field notes revealed the positive development in expressive emotions, social engagement, and decline in looking around. Outside class parent and school behavioral specialist reported the improved ability to self-regulate stress using lion's breath and super brain. These findings indicate an improvement in behaviors that influenced the physical performance, emotional expression, and social interaction after yoga training for this child.
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PMID:Effects of multisensory yoga on behavior in a male child with Apert and Asperger syndrome. 2686 77

Infertility and fecundity problems concern 10-18% of partners in their reproductive years compromising around one million females and males in Poland. Research and analysis of factors that affect male fertility are limited, especially, regarding the age of the father and determining the age at which quality of semen decreases. Age of the father has greater impact than maternal age, on cases of sporadic autosomal dominant congenital diseases such as Apert, Crouzon, Pfeiffer, Noonan and Costello syndromes, multiple endocrine neoplasia (types 2A and 2B) and achondroplasia. However, there are only a few reports taking paternal advanced age into consideration for pre-mature birth, low Apgar scores or admission to a neonatal intensive care department. Paternal age increases the frequency of congenital diseases such as heart malformations as well as oral, palate and lip cleft. Moreover, mental disorders (autism, schizophrenia, bipolar disorder, low IQ level as well as ADHD) also occur more frequently in advanced father's age. Advanced paternal age is defined differently in every research. It depends on disorders in offspring we are talking about. Paternal age has an impact on child's health and development and it is as significant as maternal age, when it comes to reproductive matters.
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PMID:Paternal age is affected by genetic abnormalities, perinatal complications and mental health of the offspring. 3204 16