This report describes a 12 year 10 month old girl with short stature and a non-mosaic 46,X,Xp+ karyotype. Her height remained below −2 SD of the mean, and her predicted adult height (143 cm) was below her target height (155·5 cm) and target range (147·5 cm−163·5 cm). Cytogenetic and molecular studies showed that the Xp+ chromosome was formed by an inverted duplication of the Xp21.3−Xp22.33 segment and was missing about 700 kb of DNA from the pseudoautosomal region distal to DXYS15. The results provide further support for the previously proposed hypothesis that the region between DXYS20 and DXYS15 is the critical region for a pseudoautosomal growth gene(s).
Pervasive Developmental Disorders (PDD) are chronic, lifelong disorders for which there is as yet no effective cure, and medical management remains a challenge for clinicians. The current report describes two patients affected by autistic disorder with associated gastrointestinal symptoms.
This report describes a case of anaplastic large cell lymphoma with the canonical t(2;5)(p23;q35) translocation in association with duplication of the short arm of the non-translocated chromosome 2, as demonstrated by two colour fluorescence in situ hybridisation. Because the tumour cells were tetraploid, these abnormalities were in duplicate, with four copies of the full length ALK gene and two copies of the t(2;5)(p23;q35) translocation. Despite multiple copies of the normal ALK gene, immunohistochemical, reverse transcriptase polymerase chain reaction, and western blot analysis demonstrated that only the fusion gene NPM/ALK was expressed and that normal ALK genes remained silent. Although based on a single case, these data indicate that structural rather than numerical abnormalities of the ALK gene are implicated in the pathogenesis of anaplastic large cell lymphomas.
A bilateral loss of short latency somatosensory evoked
potentials (SSEPs) after head trauma or non-traumatic brain damage is
normally associated with a deleterious neurological outcome. An
adequate recovery in reported in two deeply comatose patients with head
trauma or severe hypertensive encephalopathy despite prolonged
bilateral loss of SSEPs over days, found in repeated recordings. Hence,
a bilateral loss of SSEPs should not be considered alone for prediction
of outcome in cerebral injury.
We report on four children of both sexes from a highly inbred family with hypotonia, spastic diplegia, microcephaly, microphthalmia, congenital cataract, optic atrophy, ptosis, kyphoscoliosis, short stature, severe mental retardation, and cerebral malformations. Six other children may also have been affected. The differential diagnosis and the possibility of a second family with the micro syndrome are discussed. Keywords: autosomal recessive; cataract; consanguinity; mental retardation
A patient with Guillain-Barré syndrome is reported on who
responded favourably to a short course treatment with the novel immunosuppressant sodium fusidate (Fucidin), given at a daily dose of
1.5 g for one week. Along with prompt and clear cut clinical improvement, treatment with Fucidin was associated with a rapid decline
in the blood concentrations of inflammatory
cytokines presumably implicated in the pathogenesis of
Guillain-Barré syndrome such as interleukin-2,
interferon-γ, and tumor necrosis factor-α. The ex vivo production
of these cytokines was also markedly diminished compared with
pretreatment values. Fucidin was well tolerated and no clinical or
biochemical side effects were seen.
This short report discusses a case of neurofibroma containing floret-like multinucleated giant cells. This being the second such case in the literature. Floret-like multinucleated giant cells have been reported in gynaecomastia and neurofibroma in neurofibromatosis type 1. These cells have been reported in uncommon soft tissue tumours including pleomorphic lipoma, giant cell collagenoma, giant cell fibroblastoma and giant cell angiofibroma. We recommend these cells to be interpreted carefully keeping in mind the rare malignant change in neurofibromas. Immunohistochemistry would help in defining the nature of such cells.
Clozapine is the drug of choice in treatment resistant schizophrenia. It reduces hospitalizations. Patients on clozapine are often co-prescribed other psychotropics. This report looks at a sample of twenty patients on clozapine. It finds that almost two thirds were on a psychotropic along with clozapine. Eight individuals were on an antidepressant; seven on an antipsychotic and five were on co-prescribed valproate. The clinical implications are discussed and a need to look at health services involving clozapine is suggested.
This report presents the detection of a heterozygous deletion at chromosome 12q14 in three unrelated patients with a similar phenotype consisting of mild mental retardation, failure to thrive in infancy, proportionate short stature and osteopoikilosis as the most characteristic features. In each case, this interstitial deletion was found using molecular karyotyping. The deletion occurred as a de novo event and varied between 3.44 and 6 megabases (Mb) in size with a 3.44 Mb common deleted region. The deleted interval was not flanked by low‐copy repeats or segmental duplications. It contains 13 RefSeq genes, including LEMD3, which was previously shown to be the causal gene for osteopoikilosis. The observation of osteopoikilosis lesions should facilitate recognition of this new microdeletion syndrome among children with failure to thrive, short stature and learning disabilities.
We report 4 chinese patients with hepatitis B e antigen-positive chronic hepatitis B achieving clearance of HBsAg by using pegylated interferon alpha-2a for less than 1 year, to provide one clinical clue for the treatment of chronic hepatitis B.
Introduction of small interfering RNAs (siRNAs) into cells results in transitory silencing of target genes with complementary sequence. Incorporating siRNAs into short-hairpin RNAs (shRNAs) or microRNA-adapted shRNAs (shRNAmir) is a popular tool for targeted gene silencing. shRNAmirs mimicking endogenous pre-microRNAs (unprocessed hairpin microRNAs) are more difficult to design and result in longer RNA molecules. The use of microRNA (miRNA) loop sequences in shRNAs as an alternative to an entire pre-microRNA structure on silencing efficiency has not been studied extensively. This report shows that loop sequences derived from native miRNAs improves the efficiency of silencing due to the processing of the shRNAs into mature siRNAs.
Genomic rearrangements are an increasingly recognized mechanism of human phenotypic variation and susceptibility to disease. Sotos syndrome is characterized by overgrowth, macrocephaly, developmental delay and advanced osseous maturation. Haploinsufficiency of NSD1, caused by inactivating point mutations or deletion copy number variants, is the only known cause of Sotos syndrome. A recurrent 2 Mb deletion has been described with variable frequency in different populations. In this study, we report two individuals of different ethnic and geographical backgrounds, with duplications reciprocal to the common Sotos syndrome deletion. Our findings provide evidence for the existence of a novel syndrome of short stature, microcephaly, delayed bone development, speech delay and mild or absent facial dysmorphism. The phenotype is remarkably opposite to that of Sotos syndrome, suggesting a role for NSD1 in the regulation of somatic growth in humans.
We report on a 10.5-year-old girl with a mild form of campomelic dysplasia. She presented with short stature of prenatal onset, dysmorphic facial features, limitation of supination and pronation of the forearms, dysplastic nails, and bone abnormalities consisting especially of cone-shaped epiphyses of the middle phalanx of the 2nd fingers, brachydactyly and clinodactyly of the middle phalanx of both 5th fingers, short 4th metacarpals, radial and femoral head subluxation, hypoplastic scapulae, humeral and ulnar epiphyseal abnormalities, unossified symphysis pubis, and a significant delay in bone age. Molecular analysis of the SOX9 gene revealed the presence of a de novo missense mutation: p.P170L (c.509C>T). Mild and surviving cases of campomelic dysplasia are reviewed.
Short stature homeobox-containing gene, MIM 312865 (SHOX) is located within the pseudoautosomal region 1 (PAR1) of the sex chromosomes. Mutations in SHOX or its downstream transcriptional regulatory elements represent the underlying molecular defect in ∼60% of Léri-Weill dyschondrosteosis (LWD) and ∼5–15% of idiopathic short stature (ISS) patients. Recently, three novel enhancer elements have been identified upstream of SHOX but to date, no PAR1 deletions upstream of SHOX have been observed that only encompass these enhancers in LWD or ISS patients. We set out to search for genetic alterations of the upstream SHOX regulatory elements in 63 LWD and 100 ISS patients with no known alteration in SHOX or the downstream enhancer regions using a specifically designed MLPA assay, which covers the PAR1 upstream of SHOX. An upstream SHOX deletion was identified in an ISS proband and her affected father. The deletion was confirmed and delimited by array-CGH, to extend ∼286 kb. The deletion included two of the upstream SHOX enhancers without affecting SHOX. The 13.3-year-old proband had proportionate short stature with normal GH and IGF-I levels. In conclusion, we have identified the first PAR1 deletion encompassing only the upstream SHOX transcription regulatory elements in a family with ISS. The loss of these elements may result in SHOX haploinsufficiency because of decreased SHOX transcription. Therefore...
Kabuki syndrome (also known as Niikawa-Kuroki syndrome) is a rare autosomal disorder, characterized by an unusual face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, mental retardation, and immunological defects. Point mutations and large intragenic deletions and duplications of the mixed lineage leukemia 2 (MLL2) and exons deletions of lysine demethylase 6A (-KDM6A) genes have been identified as its underlying causes. We report on the first description of a Moroccan Kabuki syndrome patient with typical facial features, developmental delay, finger pads, and other anomalies carrying a novel splice site mutation in the MLL2 gene that produces a truncated and likely pathogenetic form of MLL2 protein.
The aim of tissue engineering is to develop functional substitutes for damaged tissues or malfunctioning organs. Since only nanomaterials can mimic the surface properties (ie, roughness) of natural tissues and have tunable properties (such as mechanical, magnetic, electrical, optical, and other properties), they are good candidates for increasing tissue growth, minimizing inflammation, and inhibiting infection. Recently, the use of nanomaterials in various tissue engineering applications has demonstrated improved tissue growth compared to what has been achieved until today with our conventional micron structured materials. This short report paper will summarize some of the more relevant advancements nanomaterials have made in regenerative medicine, specifically improving bone and bladder tissue growth. Moreover, this short report paper will also address the continued potential risks and toxicity concerns, which need to be accurately addressed by the use of nanomaterials. Lastly, this paper will emphasize a new field, picotechnology, in which researchers are altering electron distributions around atoms to promote surface energy to achieve similar increased tissue growth, decreased inflammation, and inhibited infection without potential nanomaterial toxicity concerns.
In presynaptic boutons, calcium (Ca2+) triggers both neurotransmitter release and short-term synaptic plasticity. Whereas synaptotagmins are known to mediate vesicle fusion through binding of high local Ca2+ to their C2 domains, the proteins that sense smaller global Ca2+ increases to produce short-term plasticity have remained elusive. Here, we identify a Ca2+ sensor for post-tetanic potentiation (PTP), a form of plasticity thought to underlie short-term memory. We find that at the functionally mature calyx of Held synapse the Ca2+-dependent protein kinase C isoforms α and β are necessary for PTP, and the expression of PKCβ in PKCαβ double knockout mice rescues PTP. Disruption of Ca2+ binding to the PKCβ C2 domain specifically prevents PTP without impairing other PKCβ-dependent forms of synaptic enhancement. We conclude that different C2-domain-containing presynaptic proteins are engaged by different Ca2+ signals, and that Ca2+ increases evoked by tetanic stimulation are sensed by PKCβ to produce PTP. DOI: http://dx.doi.org/10.7554/eLife.03011.001
The short report describes the development from page to stage of a work of theatre based on an ethnographic study. The originating research focused on the work of health care assistants (nurse's aides) whose direct impact on the quality of life of highly dependent people is often overlooked. The research followed hospital personnel on wards specialising in the 'challenging behaviour' associated with dementia in central England. Conventional research outputs failed to engage the health care assistants themselves, so we turned to theatre to remedy this. The development of the field notes into theatre was characterised by the artistic freedom given to the playwright, in contrast to more data-led approaches to theatre making. The account of the process of creating the play, Inside Out of Mind, is followed a description of how the work was received by specialist and general audiences totalling 2000+. The discussion seeks to locate the whole enterprise in relation to the field of research-based theatre and explores how the production and its associated learning events relate to definitions of research-based theatre in the light of recent attempts to encapsulate this broad and diverse methodology.
The Adult/Adolescent Vaccination Report Card (VRC) was developed and validated by Merck in 1998 for use in vaccine clinical trials to collect information from trial subjects on complaints for both local and systemic events after vaccination. This short report describes the revision to the original validated VRC in order to align with the guidelines outlined in the 2007 FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Since the VRC elicits trial subjects' self-reports of any adverse experiences (AE) occurring post vaccination, it was important that subsequent modifications of the VRC retained the original user-friendly characteristics while gathering the appropriate information to align with the FDA Guidance. A convenience sample of 15 participants (71% females, 87% white and mean (SD) age 45 (13) years was recruited to obtain feedback in order to revise the Adult/Adolescent VRC. Based on the feedback received, the following were slightly revised: ruler for the measurements of local systemic reactions, severity ratings, and general instructions. The revised VRC is currently being used in Merck vaccine clinical trials.
Mutations in the α-subunit of cardiac sodium channel gene SCN5A can lead to the overlapping phenotypes of both the Brugada and type 3 long QT syndromes. However, the combination of Brugada and a short QT phenotype resulting from mutation in SCN5A has not previously been described. A man with concomitant Brugada-like and short QT electrocardiogram (ECG) was identified and the SCN5A gene was sequenced. Whole-cell patch clamp analysis of human embryo kidney (HEK) 293 cells expressing a SCN5A channel with the patient's sequence was used to investigate the biophysical properties of the channel. The patient with the family history of sudden death showed Brugada-like and short QT interval ECG. Sequence anlaysis of the coding region of the SCN5A gene, identified a G to A heterozygous missense mutation at nucleotide site 2066 that resulted in a amino-acid substitution of arginine to histidine at amino-acid site 689 (R689H). Patch clamp analysis showed that the R689H failed to generate current when heterologously expressed in HEK293 cells, indicating it was a loss-of-function mutation. Our finding firstly showes that a heterozygous missense mutation R689H in SCN5A gene results in the loss of protein function and the coexistents of the Brugada-like and short QT interval ECG phenotypes.