Large Fermi surface in pristine kagome metal CsV3Sb5 and enhanced quasiparticle effective masses.

The kagome metal CsV[Formula: see text]Sb[Formula: see text] is an ideal platform to study the interplay between topology and electron correlation. To understand the fermiology of CsV[Formula: see text]Sb[Formula: see text], intensive quantum oscillation (QO) studies at ambient pressure have been conducted. However, due to the Fermi surface reconstruction by the complicated charge density wave (CDW) order, the QO spectrum is exceedingly complex, hindering a complete understanding of the fermiology. Here, we directly map the Fermi surface of the pristine CsV[Formula: see text]Sb[Formula: see text] by measuring Shubnikov-de Haas QOs up to 29 T under pressure, where the CDW order is completely suppressed. The QO spectrum of the pristine CsV[Formula: see text]Sb[Formula: see text] is significantly simpler than the one in the CDW phase, and the detected oscillation frequencies agree well with our density functional theory calculations. In particular, a frequency as large as 8,200 T is detected. Pressure-dependent QO studies further reveal a weak but noticeable enhancement of the quasiparticle effective masses on approaching the critical pressure where the CDW order disappears, hinting at the presence of quantum fluctuations. Our high-pressure QO results reveal the large, unreconstructed Fermi surface of CsV[Formula: see text]Sb[Formula: see text], paving the way to understanding the parent state of this intriguing metal in which the electrons can be organized into different ordered states.

Ambiguous genitalia, impaired steroidogenesis, and Antley-Bixler syndrome in a patient with P450 oxidoreductase deficiency.

Cytochrome P450 oxidoreductase deficiency is a recently established autosomal recessive disease characterised by ambiguous genitalia, impaired steroidogenesis, and skeletal malformations, referred to as Antley-Bixler syndrome. Clinical manifestations in affected patients are highly variable. We report on a girl with P450 oxidoreductase deficiency who presented with virilisation at birth. There was transient maternal virilisation during pregnancy as well. She was initially diagnosed with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency and/or aromatase deficiency. At 1 year of age, skeletal abnormalities suggestive of Antley-Bixler syndrome were detected. Molecular analysis of the fibroblast growth factor receptor 2 (FGFR2) gene was normal but POR gene analysis showed that she was homozygous for an R457H missense mutation. The diagnosis, P450 oxidoreductase deficiency, was confirmed. Results of her endocrine studies and urinary steroid profiling are also presented.

Severe neonatal manifestations of Costello syndrome.

BACKGROUND: Costello syndrome (CS) is due to mutations in HRAS, with the most common mutation being c.34G>A (p.G12S), found in most patients in all the published series. A small number of less common mutations have been reported. POPULATION STUDIED: HRAS mutation analysis has been undertaken in 74 predominantly British patients with a possible diagnosis of CS. A HRAS mutation was found in 27 patients, 15 of whom have been previously reported. PHENOTYPE ANALYSIS: Four cases had an unusually severe phenotype, associated in three cases with two unusual mutations, c.35G>A, p.G12D in two cases and c.34G>T, p.G12C in the other. Hypoglycaemia, renal abnormalities, severe early cardiomyopathy, congenital lung and airway abnormalities, pleural and pericardial effusion, chylous ascites and pulmonary lymphangectasia are confirmed as part of the clinical spectrum seen in CS. A lung pathology resembling alveolar capillary dysplasia is reported in one case. CONCLUSION: These cases illustrate that the diagnosis of CS may be difficult in the newborn period, and should be considered in the differential diagnosis of the sick newborn infant with multisystem disease. Study of more cases will be required to establish if there is a definite association between severe disease and less common mutations.

A study on body weight perception and weight control behaviours among adolescents in Hong Kong.

OBJECTIVE: To examine the relationships between body weight perceptions, estimated body mass index, gender, and weight control behaviours. DESIGN: Cross-sectional survey. SETTING: Three secondary schools in Hong Kong. PARTICIPANTS: A total of 1132 secondary school forms 1 and 3 students. MAIN OUTCOME MEASURES: The strength of agreement between perceived weight and estimated body mass index, and the association between perceived weight, estimated body mass index, and weight control behaviours. RESULTS: A total of 14% of students were estimated to be overweight or obese. The agreement between actual (estimated) body mass index and perceived weight was poor in females and fair in males (Kappa 0.137 and 0.225, respectively). In females, there was no evidence of a relationship between body mass index and weight control behaviours. However, there was a relationship between perceived weight and weight control behaviours such that females who perceived themselves as overweight were more likely to exercise, restrict caloric intake, self medicate with diet pills, purge, or use laxatives. In males, there was evidence of a relationship between perceived weight, body mass index, and weight control behaviours. Males who perceived themselves as overweight or were overweight, were more likely to exercise or restrict caloric intake. CONCLUSIONS: Body weight perceptions are not in agreement with actual weight in adolescents. This discrepancy is more marked in females who use a variety of weight control behaviours. These behaviours are motivated by perceived weight rather than actual (estimated) body mass index. Overweight adolescents should be encouraged to adopt appropriate weight control behaviours for their health needs.

Rec-mediated recombinational hot spot activity in bacteriophage lambda. II. A mutation which causes hot spot activity.

Crosses have been performed which identify phage mutants (chi) which cause recombinational hot spot activity in lambda. The hot spot activity is found in crosses of red(-) gam(-) chi(-) strains in rec(+) hosts; in the crosses reported here, both the chi(-) mutations and the hot spot are located near the right end of the chromosome. The hot spot occurs in standard crosses as well as under conditions which block DNA synthesis, and is dependent on a functional host recB gene.-The chi mutation is shown to be dominant, but the tests do not show whether chi is a gene or a site.

Cytogenetic analysis of patients with primary and secondary amenorrhoea in Hong Kong: retrospective study.

OBJECTIVE: To estimate the incidence and type of chromosomal abnormalities in patients with primary and secondary amenorrhoea in Hong Kong. DESIGN: Cytogenetic analysis and retrospective review. SETTING: Clinical Genetic Service, Department of Health, Hong Kong. PATIENTS: Case records of 549 patients with either primary (n=237) or secondary (n=312) amenorrhoea referred to the Clinical Genetic Service from 1 January 1991 to 30 April 2002 were reviewed. All these patients with amenorrhoea would have karyotyping (G banding) performed. MAIN OUTCOME MEASURES: Clinical characteristics of patients, and incidence and type of chromosomal abnormalities in the local population. RESULTS: Sex chromosome anomaly was found in 24.5% and 9.9%, respectively, of women with primary and secondary amenorrhoea. In those with primary amenorrhoea, male karyotype was identified in 8.4% and X-chromosome abnormalities in 16.0%. CONCLUSION: The incidence of chromosomal abnormalities in women with amenorrhoea is similar to that reported in the literature. Chromosomal abnormalities are identified often enough to warrant karyotyping of all women with amenorrhoea.

Chromosomal abnormalities and FMR1 gene premutation in Chinese women with premature menopause.

OBJECTIVE: To study the prevalence of chromosomal abnormalities and FMR1 gene premutation in Chinese women with premature menopause in Hong Kong. DESIGN: Retrospective study. SETTING: Clinical Genetic Service, Hong Kong. PARTICIPANTS: Chinese women with premature menopause referred for cytogenetic study from January 1983 to November 2003. MAIN OUTCOME MEASURES: Chromosomal abnormalities, FMR1 gene premutation. RESULTS: Chromosomal abnormalities were present in 15.6% of Chinese women who suffered premature menopause. X-chromosome abnormality was involved in over 80% of cases. FMR1 gene premutation was present in 0.86% of 116 cases screened for this abnormality. The predominance of X-chromosome abnormality accounted for the shorter stature, younger menopausal age, and higher prevalence of dysmorphic features among the cytogenetically abnormal patients. However, on logistic regression, no clinical feature was significantly correlated with cytogenetic abnormality. CONCLUSIONS: The prevalence of chromosomal abnormalities among Hong Kong Chinese women who suffer premature menopause was comparable with that of Caucasian and Chinese populations elsewhere. Because clinical features are poor predictors of cytogenetic abnormality, a pragmatic approach to screening is advocated. The carrier rate of fragile X premutation in these women appeared lower than that of Caucasians. Nevertheless, a search for FMR1 gene premutation, in addition to conventional chromosomal study, has important implication for prenatal diagnosis and fertility management for the extended family.

NSD1 mutations generate a genome-wide DNA methylation signature.

Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is an overgrowth/intellectual disability syndrome caused by mutations in a histone methyltransferase, NSD1. As layered epigenetic modifications are often interdependent, we propose that pathogenic NSD1 mutations have a genome-wide impact on the most stable epigenetic mark, DNA methylation (DNAm). By interrogating DNAm in SS patients, we identify a genome-wide, highly significant NSD1(+/-)-specific signature that differentiates pathogenic NSD1 mutations from controls, benign NSD1 variants and the clinically overlapping Weaver syndrome. Validation studies of independent cohorts of SS and controls assigned 100% of these samples correctly. This highly specific and sensitive NSD1(+/-) signature encompasses genes that function in cellular morphogenesis and neuronal differentiation, reflecting cardinal features of the SS phenotype. The identification of SS-specific genome-wide DNAm alterations will facilitate both the elucidation of the molecular pathophysiology of SS and the development of improved diagnostic testing.

Global regulation of expression of antifungal factors by a Pseudomonas fluorescens biological control strain.

The root-colonizing bacterium Pseudomonas fluorescens BL915 protects a variety of seedlings from damping-off disease caused by the fungal pathogen Rhizoctonia solani. Spontaneous pleiotropic mutants of P. fluorescens strain BL915 which fail to synthesize antifungal factors such as chitinase, cyanide, and pyrrolnitrin and exhibit altered colony morphology were isolated. Such mutants fail to inhibit the growth of R. solani in vitro, and their biological control capability is sharply reduced. We characterized a genomic DNA fragment from strain BL915 which, when introduced into these pleiotropic mutants, restored the lost functions, the wild-type colony morphology, and bio-control activity. DNA sequence analysis of the genomic fragment revealed the presence of genes homologous to those of numerous bacterial global regulatory systems and identified a cluster of genes identical in organization to the Escherichia coli gene cluster consisting of uvrY, uvrC, pgsA, and glyW. Coordinate biosynthesis of multiple antifungal products in some heterologous Pseudomonas strains in response to the introduction of the strain BL915 genomic fragment confirmed the regulatory nature of sequences contained on this fragment. Further genetic analysis indicated a gene homologous to response regulators of bacterial two-component systems was sufficient to complement the pleiotropic mutants and to activate antifungal genes in heterologous strains. Marker exchange of a truncated version of this gene into the P. fluorescens BL915 chromosome generated pleiotropic mutants indistinguishable from the original spontaneous mutants. Cloning and sequencing of the response regulator gene from several spontaneous mutants allowed identification of various nucleotide changes associated with the gene in such mutants.

Burton skeletal dysplasia: the second case report.

We describe a 2-year-old girl with clinical and radiological findings of Burton skeletal dysplasia. This rare disorder shows some similarities to Kniest dysplasia. Short stature, joint stiffness, microstomia, and pursed lips are characteristic clinical findings. Platyspondyly with cervical kyphosis, but no coronal clefts, and bowing of the long bones are distinctive radiographic findings.

Interstitial Dup(1p) with findings of Kabuki make-up syndrome.

We describe a male patient with interstitial duplication of the short arm of chromosome 1 with breakpoints involving 1p13.1 and 1p22.1. The patient presented with some clinical findings of Kabuki make-up syndrome (KMS), including mental retardation, small head, eversion of the lateral part of lower eyelids, epicanthic folds, lateral flare of the eyebrows, short columella, and persistent fetal finger pads. This cytogenetic finding may provide clues for gene mapping of the syndrome.

Trinucleotide CGG repeat in the FMR1 gene in Chinese mentally retarded patients.

The fragile X syndrome of mental retardation is related to the number of trinucleotide CGG repeats at the 5'-untranslated region of the FMR1 gene located on the X-chromosome. We have studied X-chromosomes from 649 unaffected Chinese subjects and 324 patients with mild mental retardation. All study subjects were unrelated. The CGG repeat number was analysed by electrophoresis of a polymerase chain reaction followed by gel transfer and hybridisation with a 32P-labeled (CCG)5 probe. The DNA samples having detectable CGG expansion were further analysed by Southern blot analysis with probe StB12.3 after restriction digestion by EcoR I and Eag I. For the unaffected Chinese subjects, a different distribution pattern of CGG allele size from Caucasians was observed. It was a bimodal pattern and the CGG repeat number ranged from 19 to 54. The most common CGG repeat allele was 29 compared with 30 in Caucasians. The second mode appeared at 36 repeats. There was mild statistical difference in the repeat patterns between the mentally retarded patients and unaffected subjects, although the essential features were similar. Among the mentally retarded patients, one male had an unmethylated full mutation and one female had a full mutation. The fragile X prevalence was 0.6%, which is lower than two previous studies in Chinese mentally retarded patients utilising cytogenetic analysis. Our results indicate that a large-scale screening program would be worthwhile to determine the prevalence of the fragile X syndrome in the Chinese population.

Acute responses of rat retina after optic nerve ligation: a biochemical and histochemical study.

The response of rat retina after optic nerve ligation was studied by biochemical and light microscope autoradiographic methods. The uptake of labelled leucine, dopamine and GABA in operated retinas were all decreased as early as 1 day after ligation. Autoradiographic morphometry revealed variations in the time course as well as in the degree of reduction of substrate uptake ability in different retinal cell layers after ligation. Findings indicate the ganglion cells and the dopaminergic cells in the outer plexiform layer are more sensitive to interruption of neuronal flow. Moreover, there may be interactions between the photoreceptors, the GABAergic and the dopaminergic cells in rat retina.

Niemann-Pick disease in the Chinese. A report of four cases in three Chinese families.

We report the first four documented cases of childhood Niemann-Pick disease in Chinese. The clinical histories and biochemical, histopathological and ultrastructural findings are given. The four children born to consanguineous parents were from three families. Three of the four cases have features of Type A disease while the younger of the affected sisters, who had over 20% residual sphingomyelinase activity, was more typical of Type B disease. Post-mortem cultured fibroblasts, when compared to control fibroblasts, revealed early features of the disease at the ultrastructural level.

Fragile X positivity in Chinese children with autistic spectrum disorder.

Chromosome analysis was performed in 105 Chinese children (96 boys, 9 girls) with autistic spectrum disorder to assess fragile X positivity. Seventy percent of these autistic children were mentally retarded. None of the children in the infantile autism group (N = 75) had fragile X positivity. Two boys in the autistic condition group (N = 30) had clinical features and chromosomal positivity for fragile X syndrome. The low (2%) prevalence rate of fragile X positivity in children with different degrees of expressivity of autistic features may be related to other factors rather than to pure autistic characteristics per se.

An analysis of multiple congenital anomaly syndromes in a Chinese population.

During an eight-year period, 4,890 index patients and their families were referred to the Clinical Genetic Service. Of the probands, 2,096 were diagnosed as suffering from multiple congenital anomaly syndromes. These represented 42.9% of the total. Ten commonest conditions accounted for 50% of patients suffering from this category of genetic diseases. A multidisciplinary approach was emphasized in the diagnosis and management.

Missense mutations of the fibrillin-1 gene in two Chinese patients with severe Marfan syndrome.

OBJECTIVE: To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene. METHODS: Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23-32, where the mutational hotspots for severe forms of Marfan syndrome are located. RESULTS: Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation. CONCLUSION: Taking advantage of the clustering phenomenon of mutations in severe forms of marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots, thus reducing the effort that would otherwise be much greater because of the size of the gene.

Williams-Beuren syndrome in the Hong Kong Chinese population: retrospective study.

OBJECTIVE: To estimate the incidence and document the clinical characteristics of Williams-Beuren syndrome in the Hong Kong Chinese population. DESIGN: Cytogenetic analysis and retrospective study. SETTING: Clinical Genetic Service, Department of Health, Hong Kong. PATIENTS: Forty-one Chinese patients with Williams-Beuren syndrome. MAIN OUTCOME MEASURES: From 1 January 1995 to 30 June 2002, fluorescence in situ hybridisation was used to confirm diagnoses in 41 cases of Williams-Beuren syndrome by detecting chromosome 7q microdeletion. Case records were reviewed, the incidence of the condition in the local population was estimated, and the main clinical characteristics were determined. RESULTS: The minimal incidence of Williams-Beuren syndrome in this locality was estimated to be approximately 1 per 23500 live births. Common dysmorphic facial features included periorbital fullness (83%), full lips (80%), a long philtrum (51%), a flat nasal bridge (41%), and abnormal teeth (37%). No patients had a stellate iris. The majority (82%) had at least one documented cardiac anomaly; among these patients, peripheral pulmonary stenosis was diagnosed in 61% and supravalvular aortic stenosis in 45%. Nearly all (93%) of the study group exhibited developmental delay. CONCLUSION: As in the West, patients with Williams-Beuren syndrome in the Hong Kong Chinese population display craniofacial dysmorphism, cardiovascular anomalies, and mental deficiency. Supravalvular aortic stenosis-the cardiac defect most commonly associated with Williams-Beuren syndrome in western countries-is less common than peripheral pulmonary stenosis in this region. Studies involving periodic cardiovascular evaluation are needed to confirm if this difference is significant.