American journal of medical genetics. Part A
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Am. J. Med. Genet. A · Jan 2010
Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to bench and back.
The RASopathies are a group of genetic syndromes caused by germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Some of these syndromes are neurofibromatosis type 1, Noonan syndrome, Costello syndrome, cardio-facio-cutaneous syndrome, LEOPARD syndrome and Legius syndrome. ⋯ The proceedings from the symposium "Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back" chronicle the timely and typical research symposium which brought together clinicians, basic scientists, physician-scientists, advocate leaders, trainees, students and individuals with Ras syndromes and their families. The goals, to discuss basic science and clinical issues, to set forth a solid framework for future research, to direct translational applications towards therapy and to set forth best practices for individuals with RASopathies were successfully meet with a commitment to begin to move towards clinical trials.
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Am. J. Med. Genet. A · Dec 2009
Review Historical ArticleDown syndrome: comments and reflections on the 50th anniversary of Lejeune's discovery.
Over the past some 160 years, the study of Down syndrome (DS) went from early efforts of differentiating it from cretinism (Séguin) to its establishment as a specific nosologic category of mental deficiency (Down) and subsequent attempts to infer its cause. DS was known to be an overwhelmingly sporadic disorder, concordant in MZ and discordant in DZ twins and associated with increased maternal reproductive age (Penrose). Beginning in the 1920s and based in part on phenotype analysis and early cytogenetic insights in Drosophilia, several clinicians (Halbertsma, Waardenburg, Bleyer, Fanconi) and the geneticist C. ⋯ Nowadays, aided with powerful molecular methods, it has become possible to attain insights into the pathogenesis of DS based on the study of many duplications/deficiencies of HSA21 in humans and ingeniously constructed cytogenetic rearrangements of MMA16 in the mouse. These suggest a complex epigenetic interaction between genes on HSA21 and many (?most) other genes in the human genome, akin to an attempt at speciation as suggested early during the last century by Blakesly in his work on Datura. Many important ongoing efforts are underway in several countries to understand the developmental biology of DS, offering hope of ultimate amelioration for those averse to pregnancy termination.
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Am. J. Med. Genet. A · Nov 2009
ReviewThe genetics of sleep disorders in humans: narcolepsy, restless legs syndrome, and obstructive sleep apnea syndrome.
Sleep disorders are a group of neurological disorders known to cause public health problems associated with interference with daily activities including cognitive problems, poor job performance and reduced productivity. There is strong evidence emerging for the presence of genes influencing sleep disorders, such as narcolepsy (NRCLP), restless legs syndrome (RLS), and obstructive sleep apnea syndrome (OSAS). NRCLP is typically characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hallucinations. ⋯ OSAS is major sleep problem characterized by recurrent episodes of upper airway collapse and obstruction during sleep. In the recent years, many research groups have attempted to identify the susceptibility and candidate genes for NRCLP, RLS, and OSAS through the sequential analyses of genetic linkage and association. The purpose of this review is to summarize some of remarkable molecular advances in sleep and sleep disorders, thereby providing a greater understanding of the complex sleep processes, and a platform for future therapeutic interventions.
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Am. J. Med. Genet. A · Nov 2009
Array-based comparative genomic hybridization (aCGH) in the genetic evaluation of stillbirth.
This study examined the utility of array-based comparative genomic hybridization (aCGH) in detecting genetic abnormalities associated with late pregnancy loss. Comparisons were made with classic cytogenetics to test whether aCGH represents a superior methodology for the clinical evaluation of stillbirth. ⋯ Among 15 tested stillborns, aCGH detected two abnormalities (trisomy 21 and an unbalanced translocation between chromosomes 3 and 10), for an overall detection rate of 13% in stillborns with malformations who had normal or unobtainable cytogenetic results. This preliminary study supports the clinical value of aCGH testing in diagnostic evaluation of stillborns with congenital anomalies.