Communicative competence and behavioural phenotype in children with Smith-Magenis syndrome

Smith-Magenis syndrome is characterized by a range of minor physical and facial abnormalities and is caused by a de novo deletion on chromosome 17. Most children function in the moderate to severe ranges of mental retardation. Results of a survey on adaptive skills, communicative competence and behavioural abnormalities in 20 children are reported. The findings suggest a strong desire to get in social contact and maintain conversations in spite of their limited cognitive processing. As a group, children with SMS are presenting with severe behavioural abnormalities, e.g. self-injury, extreme irritability, ritualistic behaviour. Behaviour problems are more severe than in other genetic syndrome groups as a comparison with Prader-Willi- and Fragile-X-syndrome children reveals. However, functional analysis suggests that it is not independent from situational variables. There is a strong need for behavioural intervention planning as part of family services.     

Microdeletion on 17p11.2 in a Smith-Magenis syndrome patient with mental retardation and congenital heart defect: first report from China

Smith-Magenis syndrome (SMS) is a rare syndrome with multiple congenital malformations, including development and mental retardation, behavioral problems and a distinct facial appearance. SMS is caused by haploinsufficiency of RAI1 (deletion or mutation of RAI1). We describe an eight-year-old female Chinese patient with multiple malformations, congenital heart defect, mental retardation, and behavioral problems (self hugging, sleeping disturbance). High-resolution genome wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in chromosome region 17p11.2. This chromosome region contains RAI1, a critical gene involved in SMS. To the best of our knowledge, this is the first report of an SMS patient in mainland China.     

Triphalangeal thumb and psychomotor retardation: a new association?

The triphalangeal thumb (TPT) is a rare malformation in which the thumb is presented as a long digit of three phalanges. We describe two brothers showing TPT and psychomotor retardation, especially in language. Difficulties in language development were also observed in children with TPT in another study. The coexistence of TPT and psychomotor retardation in those patients and in the two patients described here suggests that TPT and psychomotor retardation could be part of a syndromic association not described previously.     

A Turkish patient with large 17p11.2 deletion presenting with Smith Magenis syndrome

Smith-Magenis syndrome (SMS), which occurs as a result of an interstitial deletion within chromosome 17p11.2-p12, is a disorder that presents itself with minor dysmorphic features, brachydactyly, short stature, hypotonia, delayed speech, cognitive deficits and neurobehavioral problems including sleep disturbances and maladaptive repetitive and self-injurious behavior. We present a girl with full SMS phenotype. G-banding cytogenetic analysis showed normal 46,XX karyotype. Whole-genome array comparative genomic hybridization (CGH) was performed due to the severity of the phenotype and the unusual features present in the patient. An interstitial deletion in 17p11.2-p12, approximately 4.73 Mb in size was determined. Characteristic physical and behavioral phenotype strongly suggested SMS. This, to the best of our knowledge is the first patient with SMS reported in Turkey. We emphasize the need for whole genome analysis in multiple congenital abnormalities/mental retardation disorders with unusual and severe phenotypes.     

Neurodevelopment in children with single-suture craniosynostosis and plagiocephaly without synostosis.

The objective of this study was to determine whether children with nonsyndromic craniosynostosis and plagiocephaly without synostosis demonstrated cognitive and psychomotor delays when compared with a standardized population sample. This was the initial assessment of a larger prospective study, which involved 21 subjects with nonsyndromic craniosynostosis (mean age, 10.9 months) and 42 subjects with plagiocephaly without synostosis (mean age, 8.4 months). Each child was assessed using the Bayley Scales of Infant Development-II (BSID-II) for cognitive and psychomotor development before therapeutic intervention (surgery for craniosynostosis and molding-helmet therapy for plagiocephaly without synostosis). The distribution of the scores was divided into four groups: accelerated, normal, mild delay, and significant delay. The distributions of the mental developmental index (MDI) and the psychomotor developmental index (PDI) were then compared with a standardized Bayley's age-matched population, using Fisher's exact chi-square test. Within the craniosynostosis group, the PDI scores were significantly different from the standardized distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the craniosynostosis group were accelerated, 43 percent were normal, 48 percent had mild delay, and 9 percent had significant delay. In contrast, the MDI scores were not statistically different (p = 0.08). Within the group with plagiocephaly without synostosis, both the PDI and MDI scores were significantly different from the normal curve distribution (p < 0.001). With regard to the PDI scores, 0 percent of the subjects in the group with plagiocephaly without synostosis were accelerated, 67 percent were normal, 20 percent had mild delay, and 13 percent had significant delay. With regard to the MDI scores, 0 percent of the subjects in this group were accelerated, 83 percent were normal, 8 percent had mild delay and 9 percent had significant delay. This study indicates that before any intervention, subjects with single-suture syndromic craniosynostosis and plagiocephaly without synostosis demonstrate delays in cognitive and psychomotor development. Continued postintervention assessments are needed to determine whether these developmental delays can be ameliorated with treatment.     

The effect of somatostatin on the production of human interferons by mononuclear cells.

Somatostatin (SMS) is a tetradecapeptide which can inhibit the secretion of a number of peptides produced by the endocrine or nervous systems. SMS 201-995 (octreotide) is a somatostatin analogue with very potent somatostatin activities. We have been investigating the effects of both SMS and octreotide on the production of human interferon (IFN). We obtained human peripheral blood mononuclear cells from normal donors and induced them to produce IFN in the presence or absence of a number of peptides possessing somatostatin activities. SMS and octreotide were shown to inhibit the secretion of INF-gamma but not IFN-alpha. Concentrations of 10(-6) M were shown to decrease yields when Concanavalin A or phytohemagglutin were used as the inducer. Higher concentrations had a progressively greater effect. No effects were observed on IFN-gamma production if interleukin 2, ionomycin, or various natural antigens were used to induce the cells. The 28-amino acid form of somatostatin had some effects on gamma IFN yields but the first 14-amino acid fragment of this peptide moiety did not. No effect of any of these compounds was observed on IFN bioactivity. These studies indicate SMS may have some regulatory action on the secretion of immunomodulators in vitro but the concentrations required are well above those encountered under physiologic circumstances, suggesting SMS may not play an important regulatory role governing such secretion in vivo.     

Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism

N-terminal acetylation of proteins is a widespread and highly conserved process. Aminoacylase 1 (ACY1; EC 3.5.14) is the most abundant of the aminoacylases, a class of enzymes involved in hydrolysis of N-acetylated proteins. Here, we present four children with genetic deficiency of ACY1. They were identified through organic acid analyses using gas chromatography-mass spectrometry, revealing increased urinary excretion of several N-acetylated amino acids, including the derivatives of methionine, glutamic acid, alanine, leucine, glycine, valine, and isoleucine. Nuclear magnetic resonance spectroscopy analysis of urine samples detected a distinct pattern of N-acetylated metabolites, consistent with ACY1 dysfunction. Functional analyses of patients' lymphoblasts demonstrated ACY1 deficiency. Mutation analysis uncovered recessive loss-of-function or missense ACY1 mutations in all four individuals affected. We conclude that ACY1 mutations in these children led to functional ACY1 deficiency and excretion of N-acetylated amino acids. Questions remain, however, as to the clinical significance of ACY1 deficiency. The ACY1-deficient individuals were ascertained through urine metabolic screening because of unspecific psychomotor delay (one subject), psychomotor delay with atrophy of the vermis and syringomyelia (one subject), marked muscular hypotonia (one subject), and follow-up for early treated biotinidase deficiency and normal clinical findings (one subject). Because ACY1 is evolutionarily conserved in fish, frog, mouse, and human and is expressed in the central nervous system (CNS) in human, a role in CNS function or development is conceivable but has yet to be demonstrated. Thus, at this point, we cannot state whether ACY1 deficiency has pathogenic significance with pleiotropic clinical expression or is simply a biochemical variant. Awareness of this new genetic entity may help both in delineating its clinical significance and in avoiding erroneous diagnoses.     

Familial deletion of 22q11.2.

We present a mother and her son, both carrying a deletion of chromosome 22q.11.2. They manifest clinical heterogeneity. The mother has schizophrenia, an IQ of 70. Tetralogy of Fallot, a hypernasal voice, but does not have the characteristic facies. Her son has mild psychomotor developmental delay. Tetralogy of Fallot and mild facial features characteristic of VCFS.     

Microduplication 22q11.2: a description of the clinical, developmental and behavioral characteristics during childhood

Microduplication 22q11.2 is a recently discovered genomic disorder. So far, targeted research on the cognitive and behavioral characteristics of individuals with this microduplication is limited. Therefore, 11 Flemish children (3-13 years old) with a microduplication 22q 1.2 were investigated in order to describe their clinical, developmental and behavioral characteristics. We measured their general intelligence, visual-motor capacities, attention, behavioral problems and characteristics of autism. In addition, there was an interview with the parents on developmental history and we reviewed available information from other specialists. The results show that the cognitive and behavioral phenotype of the children with microduplication 22q.11.2 is very wide and heterogeneous. Some of the children have a cognitively nearly normal development whereas others are more severely affected. All children had some degree of developmental delay and some of them have an intellectual disability. The most common clinical features include congenital malformations such as heart defects and cleft lip, feeding problems, hearing impairment and facial dysmorphism. The most common non-medical problems are learning difficulties, motor impairment, attention deficits, social problems and behavioral problems. There is no correlation between the size of the duplication and the phenotype.     

LabPush: A Pilot Study of Providing Remote Clinics with Laboratory Results via Short Message Service (SMS) in Swaziland,Africa

Background

Turnaround time (TAT) is an important indicator of laboratory performance. It is often difficult to achieve fast TAT for blood tests conducted at clinics in developing countries. This is because clinics where the patient is treated are often far away from the laboratory, and transporting blood samples and test results between the two locations creates significant delay.Recent efforts have sought to mitigate this problem by using Short Message Service (SMS) to reduce TAT. Studies reporting the impact of this technique have not been published in scientific literature however. In this paper we present a study of LabPush, a system developed to test whether SMS delivery of HIV related laboratory results to clinics could shorten TAT time significantly.

Method

LapPush was implemented in six clinics of the Kingdom of Swaziland. SMS results were sent out from the laboratory as a supplement to normal transport of paper results. Each clinic was equipped with a mobile phone to receive SMS results. The laboratory that processes the blood tests was equipped with a system for digital input of results, and transmission of results via SMS to the clinics.

Results

Laboratory results were received for 1041 different clinical cases. The total number of SMS records received (1032) was higher than that of paper records (965), indicating a higher loss rate for paper records. A statistical comparison of TAT for SMS and paper reports indicates a statistically significant improvement for SMS. Results were more positive for more rural clinics, and an urban clinic with high workload.

Conclusion

SMS can be used to reduce TAT for blood tests taken at clinics in developing countries. Benefits are likely to be greater at clinics that are further away from laboratories, due to the difficulties this imposes on transport of paper records.     

The human homologue of the Drosophila melanogaster flightless-I gene (flil) maps within the Smith-Magenis microdeletion critical region in 17p11.2.

The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances, and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date, no protein-encoding gene has been mapped to the SMS critical region. Recently, the Drosophila melanogaster flightless-I gene, fliI, and the homologous human cDNA have been isolated. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for FISH, which localized this gene to the 17p11.2 region. Somatic-cell hybrid-panel mapping further localized this gene to the SMS critical region. Southern blot analysis of somatic-cell hybrids and/or FISH analysis of lymphoblastoid cell lines from 12 SMS patients demonstrates the deletion of one copy of FLI in all SMS patients analyzed.     

Inhibition of sphingomyelin synthase (SMS) affects intracellular sphingomyelin accumulation and plasma membrane lipid organization

Sphingomyelin plays a very important role both in cell membrane formation that may well have an impact on the development of diseases like atherosclerosis and diabetes. However, the molecular mechanism that governs intracellular and plasma membrane SM levels is largely unknown. Recently, two isoforms of sphingomyelin synthase (SMS1 and SMS2), the last enzyme for SM de novo synthesis, have been cloned. We have hypothesized that SMS1 and SMS2 are the two most likely candidates responsible for the SM levels in the cells and on the plasma membrane. To test this hypothesis, cultured cells were treated with tricyclodecan-9-yl-xanthogenate (D609), an inhibitor of SMS, or with SMS1 and SMS2 siRNAs. Cells were then pulsed with [14C]-L-serine (a precursor of all sphingolipids). SMS activity and [14C]-SM in the cells were monitored. We found that SMS activity was significantly decreased in cells after D609 or SMS siRNA treatment, compared with controls. SMS inhibition by D609 or SMS siRNAs significantly decreased intracellular [14C]-SM levels. We measured cellular lipid levels, including SM, ceramide, phosphatidylcholine, and diacylglycerol and found that SMS1 and SMS2 siRNA treatment caused a significant decrease of SM levels (20% and 11%, respectively), compared to control siRNA treatment; SMS1 but not SMS2 siRNA treatment caused a significant increase of ceramide levels (10%). There was a decreasing tendency for diacylglycerol levels after both SMS1 and SMS2 siRNA treatment, however, it was not statistical significant. As shown by lipid rafts isolation and lipid determination, SMS1 and SMS2 siRNA treatment led to a decrease of SM content in detergent-resistant lipid rafts on the cell membrane. Furthermore, SMS1 and SMS2 siRNA-treated cells had a stronger resistance than did control siRNA-treated cells to lysenin (a protein that causes cell lysis due to its affinity for plasma membrane SM). These results indicate that both SMS1 and SMS2 contribute to SM de novo synthesis and control SM levels in the cells and on the cell membrane including plasma membrane, implying an important relationship between SMS activity and cell functions.     

Duplications of proximal 16q flanked by heterochromatin are not euchromatic variants and show no evidence of heterochromatic position effect

Extra euchromatic material was found within the major heterochromatic block of chromosome 16 (16qh) in one de novo case and seven members of two families. In contrast to the euchromatic variants of chromosome 9 (9qh), which are derived from pericentromeric euchromatin, molecular cytogenetics confirmed that these duplications were of 16q11.2-->q12.2 in the de novo case, of 16q11.2-->q13 in three members of family 1 and 16q11.2-->q12.1 in four members of family 2. The duplication had arisen as a post-zygotic mitotic event in the mother of family 1 and been transmitted paternally in family 2. An insertional mechanism of origin is proposed for the duplications in case 1 and family 1. Expression at the 16q13 matrix metalloproteinase-2 (MMP2)locus in families 1 and 2 was proportional to genomic copy number and not therefore consistent with position effect silencing due to the flanking blocks of heterochromatin. We conclude that proximal 16q duplications within 16qh are not novel euchromatic variants but associated with a variable phenotype including developmental delay, speech delay, learning difficulties and behavioural problems. The behavioural problems in families ascertained through affected children are much less severe than those encountered in previous patients ascertained as adults.     

Children with a 22q11 deletion versus children with a speech-language impairment and learning disability: behavior during primary school age

Children with a 22q11 deletion versus children with a speech-language impairment and learning disability: behavior during primary school age: Common behavioral features described in children with the Velo-Cardio-Facial syndrome (VCFS) (del 22q11) are problems with attention and concentration, extremes in behavior and social problems, especially in relationship with peers. At present, it is unclear whether these behavioral manifestations are directly related to the chromosomal anomaly or related to other manifestations of the syndrome such as developmental delay and speech-language delay. This study describes for the first time the behavior of young primary school aged children with a del22q11 compared to a control group of children matched for age, sex and mental level, with similar developmental problems (speech-language impairment plus learning disability: SLI + LD) but without a del22q11 or any other known genetic condition. Parents and teachers evaluated the children's behavior with standardized questionnaires (CBCL; TRF). Results indicate that most of the behaviors are similar across both groups. The only differences found are in the field of and . Children with a del22q11 have a stronger tendency to withdraw from others, whereas children with a SLI+LD seem to be more aggressive.     

Efficient push-based packet scheduling for Peer-to-Peer live streaming

Content scheduling is a key component of Peer-to-Peer (P2P) networks. The problem is how to schedule the content delivery to the children peers with multiple parents to improve the overall performance of the systems. The challenge is to design a scheme with low delay and low bandwidth utilization. Most of recent works propose pull-based schemes, whose processes for periodically advertising and requesting on per-packet basic lead to long delay. However, long playback delay is undesirable for live streaming and TV shows. In this paper, we formulate the scheduling problems as to minimize the playback delay due to scheduling. To solve the problem and address the packet redundancy and disorder packet arrival issues, we propose a novel push-based scheme. In our scheme, parents push packets to their children in a given interval pattern as soon as the packets are received, and children feed back network condition changes with an interval pattern when necessary. The scheme eliminates the processes of buffer advertising and packet requesting, and reduces control traffic, delivery delay and playback delay much more than the pull-based schemes. We provide an efficient scheduling algorithm and its implementation for simulation. The simulation results show that our scheme outperforms other pull-based schemes significantly.     

Effect of spent mushroom compost tea on mycelial growth and yield of button mushroom (Agaricus bisporus)

Preliminary studies suggested that the use of compost tea made from spent mushroom substrate (SMS) may be regarded as a potential method for biologically controlling dry bubble disease in button mushroom. The aim of this study was to assess the effect of SMS compost tea on the host, the button mushroom, to ascertain whether the addition of these water extracts has a toxic effect on Agaricus bisporus mycelium growth and on mushroom yield. In vitro experiments showed that the addition of SMS compost tea to the culture medium inoculated with a mushroom spawn grain did not have an inhibitory effect on A. bisporus mycelial growth. The effect of compost teas on the quantitative production parameters of A. bisporus (yield, unitary weight, biological efficiency and earliness) was tested in a cropping trial, applying the compost teas to the casing in three different drench applications. Quantitative production parameters were not significantly affected by the compost tea treatments although there was a slight delay of 0.8-1.4 days in the harvest time of the first flush. These results suggest that compost teas have no fungitoxic effect on A. bisporus so that they can be considered a suitable biocontrol substance for the control of dry bubble disease.     

食用菌菌糠综合利用研究进展

中国是食用菌生产第一大国,每年产生约1亿多t菌糠,菌糠中含有大量的粗纤维和多糖等物质,但大部分菌糠都被当作废弃物直接丢弃或焚烧,造成严重的环境污染和资源浪费,同时也不符合我国新时期的环保政策,如何变废为宝,科学、环保、经济、合理地利用菌糠成为食用菌产业健康发展的重要环节。本文通过对食用菌菌糠综合利用的方式和现状进行阐述,探讨菌糠利用存在的主要问题,对未来菌糠利用的方向和发展趋势进行展望,为食用菌菌糠的高效利用提供参考和理论依据。     

Argininosuccinic aciduria. A new case revealed by psychiatric disorders

The case of a 4 years old boy, hospitalized for an unexplained coma, is reported. He is the first child of a non-consanguin couple. The psychomotor development of this child was considered as normal up to the age of 18 months; then, a delay in language development, behaviour disorders with an important instability interrupted by episodes of somnolence, were observed. This child was treated for psychotic disorders. At the age of 3 and half, he had two episodes of seizures associated with fever. He was hospitalized for a 24 hours coma (4 years old). An hepatomegaly and a dry, brittle hair were then observed. Hyperammonemia was made obvious by a protein tolerance test. The diagnosis of argininosuccinate lyase (ASAL) deficiency was based on the increased levels of ASA in plasma and urine. The deficiency was proved by a fibroblast culture. With protein restriction, hepatomegaly disappeared, hair became normal, the behaviour disorders and the delay in language development was improved. However, some school difficulties persist. This case shows that an hereditary metabolic syndrome can be revealed by psychotic like symptoms in childhood.