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      Sleep Disorders in Childhood Neurogenetic Disorders

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          Abstract

          Genetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as “rare disease,” but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader–Willi syndrome, Smith–Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions.

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          Health supervision for children with Down syndrome.

          These guidelines are designed to assist the pediatrician in caring for the child in whom a diagnosis of Down syndrome has been confirmed by chromosome analysis. Although a pediatrician's initial contact with the child is usually during infancy, occasionally the pregnant woman who has been given a prenatal diagnosis of Down syndrome will be referred for review of the condition and the genetic counseling provided. Therefore, this report offers guidance for this situation as well.
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            The DNA sequence of human chromosome 21.

            Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.
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              Mechanisms and consequences of somatic mosaicism in humans.

              Somatic mosaicism -- the presence of genetically distinct populations of somatic cells in a given organism -- is frequently masked, but it can also result in major phenotypic changes and reveal the expression of otherwise lethal genetic mutations. Mosaicism can be caused by DNA mutations, epigenetic alterations of DNA, chromosomal abnormalities and the spontaneous reversion of inherited mutations. In this review, we discuss the human disorders that result from somatic mosaicism, as well as the molecular genetic mechanisms by which they arise. Specifically, we emphasize the role of selection in the phenotypic manifestations of mosaicism.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Children (Basel)
                Children (Basel)
                children
                Children
                MDPI
                2227-9067
                12 September 2017
                September 2017
                : 4
                : 9
                : 82
                Affiliations
                Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; vaughnb@ 123456neurology.unc.edu (B.V.V.); zheng_fan@ 123456med.unc.edu (Z.F.)
                Author notes
                [* ]Correspondence: laura.dosier@ 123456unchealth.unc.edu ; Tel.: +1-984-974-3294; Fax: +1-919-966-2292
                Article
                children-04-00082
                10.3390/children4090082
                5615272
                28895939
                50d9a5dd-368d-4d91-8216-52f8bb8ffaf5
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 June 2017
                : 21 August 2017
                Categories
                Review

                neurogenetic,sleep,neurodevelopmental,angelman,down syndrome,trisomy 21,smith–magenis,muchopolysaccharidosis,achondroplasia,duchenne,congenital central hypoventilation

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