Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The region of chromosome 21 between genes CBR and ERG (CBR-ERG region), which spans 2.5 Mb on 21q22.2, has been defined by analysis of patients with partial trisomy 21. It contributes significantly to the pathogenesis of many characteristics of Down syndrome, including morphological features, hypotonia, and mental retardation. Cosmid contigs covering 80% of the region were constructed and EcoRI maps produced. These cosmids were used for exon trapping and cDNA selection from three cDNA libraries (fetal brain, fetal liver, and adult skeletal muscle). Isolated exons and cDNAs were mapped on the EcoRI map, organized into contigs, sequenced, and used as probes for Northern blot analysis of RNA from fetal and adult tissues. We identified 27 genuine or highly probable transcriptional units evenly distributed along the CBR-ERG region. Eight of the transcriptional units are known genes.
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PMID:Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21 involved in Down syndrome. 950 11

The objective of the study was to elucidate if individuals with Down's syndrome (DS) are likely to experience an increased risk of osteoporosis with advancing age, in addition to precocious aging and their skeletal anomalies. Bone mineral density (BMD) was measured in 22 home-reared adults (9 males and 13 females; age 26.22 +/- 4.45 and 23.65 +/- 3.23 years, respectively) by dual energy X-ray absorptiometry (DXA). The BMD of the second to fourth lumbar vertebrae was measured in posteroanterior projection and the mean density expressed as grams per square centimetre. The BMD of DS individuals was compared with 27 control subjects (12 males and 15 females) of the same age (age 24.16 +/- 3.46 and 23.86 +/- 2.92 years, respectively). The results showed that the BMD of the lumbar spine in the males as well as in the females with DS was significantly lower than that in their control counter-parts (p < 0.001). Comparing the DS males with the females, the BMD was lower in the males at a level of 9%. Factors that contribute to this disorder may be mainly the muscular hypotonia, the sedentary life-style and the accompanying diseases which frequently observed in the syndrome. Future studies must be focused on the biochemistry of bone metabolism, the evaluation of gonadal, thyroid and parathyroid function, and the genes of the extra chromosome 21.
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PMID:Bone mineral density in adults with Down's syndrome. 1035 78

A nine-month-old boy, with functional disomy for Xq26-qter and multiple congenital abnormalities, is reported. The boy had severe pre- and postnatal growth retardation, profound developmental delay, hypotonia, microcephaly, agenesis of the corpus callosum, dysmorphic facial features, cryptorchidism, and left multidysplastic kidney. He developed feeding difficulties and infantile spasms. G-banding analysis of his chromosomes showed additional material on the short arm of chromosome 21. His parents refused to submit to chromosome analysis. Analysis with chromosome microdissection followed by reverse and forward chromosome painting indicated his karyotype as 46,XY,der(21)t(X;21)(q26;p11.2). This is the first description of pure functional disomy for Xq26-qter due to an unbalanced X-autosome translocation.
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PMID:Functional disomy for Xq26.3-qter in a boy with an unbalanced t(X;21)(q26.3;p11.2) translocation. 1124 67

Down's syndrome (DS) is a major cause of mental retardation, hypotonia and delayed development. Murine models of DS carrying large murine or human genomic fragments show motor alterations and memory deficits. The specific genes responsible for these phenotypic alterations have not yet been defined. DYRK1A, the human homolog of the Drosophila minibrain gene, maps to the DS critical region of human chromosome 21 and is overexpressed in DS fetal brain. DYRK1A encodes a serine-threonine kinase, probably involved in neuroblast proliferation. Mutant Drosophila minibrain flies have a reduction in both optic lobes and central brain, showing learning deficits and hypoactivity. We have generated transgenic mice (TgDyrk1A) overexpressing the full-length cDNA of Dyrk1A. TgDyrk1A mice exhibit delayed cranio-caudal maturation with functional consequences in neuromotor development. TgDyrk1A mice also show altered motor skill acquisition and hyperactivity, which is maintained to adulthood. In the Morris water maze, TgDyrk1A mice show a significant impairment in spatial learning and cognitive flexibility, indicative of hippocampal and prefrontal cortex dysfunction. In the more complex repeated reversal learning paradigm, this defect turned out to be specifically related to reference memory, whereas working memory was almost unimpaired. These alterations are comparable with those found in the partial trisomy chromosome 16 murine models of DS and suggest a causative role of DYRK1A in mental retardation and in motor anomalies of DS.
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PMID:Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. 1155 28

The availability of the recently published DNA sequence of human chromosome 21 (HSA21) is a landmark contribution that will have an immediate impact on the study of the role of specific genes to Down syndrome (DS). Trisomy 21 or DS is the only autosomal aneuploidy that is not lethal in the fetal or early postnatal period. DS phenotypes show variable penetrance, affecting many different organs, including brain (mental retardation, early onset of Alzheimer's disease, AD), muscle (hypotonia), skeleton, and blood. DS phenotypes may stem directly from the cumulative effect of overexpression of specific HSA21 gene products or indirectly through the interaction of these gene products with the whole genome, transcriptome, or proteome. Mouse genetic models have played an important role in the elucidation of the contribution of specific genes to the DS phenotype. To date, the strategies used for modeling DS in mice have been three: (1) to assess single-gene contributions to DS phenotype, using transgenic techniques to create models overexpressing single or combinations of genes, (2) to assess the effects of overexpressing large foreign DNA pieces, introduced on yeast artificial chromosomes (YACs) or bacterial artificial chromosomes (BACs) into transgenic mice, and (3) mouse trisomies that carry all or part of MMU16, which has regions of conserved homology with HSA21. Here we review the existing murine models and the relevance of their contribution to DS research.
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PMID:Murine models for Down syndrome. 1156 19

We report on a patient with a full monosomy 21 (FM21) prenatally diagnosed in cord fetal blood, and subsequently confirmed in other tissues. Subtle chromosomal translocations of chromosome 21, were ruled-out by FISH using both painting and 21q telomeric probes. Microsatellites analysis demonstrated the paternal origin of the single chromosome. The propositus showed at 32 weeks of gestation a severe intrauterine growth retardation and microcephaly. He was born with multiple congenital malformations, hypotonia, microcephaly, bilateral microphthalmia (more severe on the left), facial dysmorphism, agenesis of the external auditory meatus, redundant skin in the neck, narrow chest, flat scrotum, cryptorchydism, hypospadias, micropene, camptodactyly, nail hypoplasia, and abnormal palmar and plantar creases. The patient died in the first day of life. At necropsy, micrencephaly, semilobar holoprosencephaly, polimicrogyria, ocular abnormalities, skeletal anomalies, congenital heart disease, and agenesis of right kidney were also observed. To our best knowledge, this case is one of the most completely patient studied with FM21.
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PMID:A prenatally diagnosed patient with full monosomy 21: ultrasound, cytogenetic, clinical, molecular, and necropsy findings. 1510 21

A 14-year-old boy was referred for a genetics evaluation after high-resolution chromosome analysis showed a small amount of extra material in the proximal long arm of chromosome 21. Five years prior, his karyotype analysis was interpreted as normal with a variant chromosome 21. The patient has short palpebral fissures, strabismus, flat antihelices of the ears, long thumbs with bilaterally absent interphalangeal creases, proximal bilateral 3/4 syndactyly, small testes, hypotonia, mental retardation, and speech problems. He has significant depression and behavioral problems including hyperactivity, aggression, and impulsivity. His 8-year-old brother has more severe behavioral disturbances and depression, but less significant mental retardation. A paternal aunt has mental retardation, is unusually docile, and appears similar to our patient. Chromosome analysis and fluorescence in situ hybridization (FISH) whole chromosome paint of chromosome 21 showed that the patient's father carries a "cryptic" balanced translocation, 46,XY, t(14;21)(q11.2;q11.2), as does the patient's paternal grandmother. Uniparental disomy studies using seven informative polymorphic nucleotide repeat markers from 14q and 21q confirmed biparental inheritance of the number 14 and 21 chromosomes for each brother, and indicate that they and the paternal aunt, all of whom inherited the der(14), are monosomic for proximal 21q and trisomic for proximal 14q. These karyotypes arose through an adjacent-2 segregation in the father on two occasions, and from the paternal grandmother on one occasion. This family is an example of recurrent malsegregation with translocations involving the acrocentrics.
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PMID:Recurrent adjacent-2 segregation of a familial t(14;21)(q11.2;q11.2): phenotypic comparison of two brothers and a paternal aunt inheriting the der(14). 1555 40

We describe a patient in whom full monosomy 21 was initially assumed from routine GTG-banded karyotyping. Re-examination with chromosome painting demonstrated an unbalanced translocation between the long arms of chromosomes 18 and 21. Fluorescence in situ hybridisation (FISH) and microsatellite marker analysis revealed partial monosomy of chromosome 21 (pter-q21) and 18(q22-qter). The patient, 18 years old at the second examination, revealed multiple dysmorphic features, genital hypoplasia, dilated cerebral ventricles, muscular hypotonia and severe mental retardation. In not one out of all patients investigated postnatally in whom an initial examination had revealed monosomy 21, this could be confirmed by FISH; in all of them, re-examination detected an unbalanced rearrangement leading to only partial monosomy 21 plus partial monosomy of another chromosome to which the distal 21q segment was attached. Thus, it is still highly likely that full monosomy 21 is incompatible with intra-uterine survival.
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PMID:Unbalanced 18q/21q translocation in a patient previously reported as monosomy 21. 1605 8

Down syndrome, the result of trisomy of chromosome 21, is one of the most common chromosomal abnormalities. Patients have a characteristic facial appearance, variable levels of intelligence and self-care skills, and a variety of associated medical conditions. Orthopaedic manifestations occur frequently; most are related to hypotonia, joint hypermobility, and ligamentous laxity. Atlanto-occipital and atlantoaxial hypermobility, as well as bony anomalies of the cervical spine, can produce atlanto-occipital and cervical instability. Methods of screening for this instability, particularly with regard to participation in sports, are a subject of controversy. Scoliosis, hip instability, slipped capital femoral epiphysis, patellar instability, and foot deformities are other musculoskeletal conditions found in patients with Down syndrome that can be challenging for the orthopaedic surgeon to treat.
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PMID:Down syndrome in children: the role of the orthopaedic surgeon. 1703 May 94

The Ts65Dn segmental mouse model of Down syndrome (DS) possesses a triplication of the section of chromosome 16 that is most homologous to the human chromosome 21 that is trisomic in DS. This model exhibits many of the characteristics of DS including small size, developmental delays, and a decline of cholinergic systems and cognitive function with age. Recent studies have shown that vasoactive intestinal peptide (VIP) systems are upregulated in aged Ts65Dn mice and that VIP dysregulation during embryogenesis is followed by the hypotonia and developmental delays as seen in both DS and in Ts65Dn mice. Additionally, astrocytes from aged Ts65Dn brains do not respond to VIP stimulation to release survival-promoting substances. To determine if VIP dysregulation is age-related in Ts65Dn mice, the current study examined VIP and VIP receptors (VPAC-1 and VPAC-2) in postnatal day 8 Ts65Dn mice. VIP and VPAC-1 expression was significantly increased in the brains of trisomic mice compared with wild-type mice. VIP-binding sites were also significantly increased in several brain areas of young Ts65Dn mice, especially in the cortex, caudate/putamen, and hippocampus. Further, in vitro treatment of normal neurons with conditioned medium from VIP-stimulated Ts65Dn astrocytes from neonatal mice did not enhance neuronal survival. This study indicates that VIP anomalies are present in neonatal Ts65Dn mice, a defect occurs in the signal transduction mechanism of the VPAC-1 VIP receptor, cortical astrocytes from neonatal brains are dysfunctional, and further, that VIP dysregulation may play a significant role in DS.
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PMID:Neonatal mice of the Down syndrome model, Ts65Dn, exhibit upregulated VIP measures and reduced responsiveness of cortical astrocytes to VIP stimulation. 1740 Nov 58


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