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PubMed2003

Analysis of natural populations of Prochlorococcus spp. in the northern Red Sea using phycoerythrin gene sequences.

Marine cyanobacteria of the genus Prochlorococcus belong to one of two ecotypes that are specifically adapted to either low light (LL) or high light (HL) conditions. Previous analyses of the differences in pigmentation and gene complement revealed that LL-adapted ecotypes carry a gene cluster to produce a functional phycoerythrin, whereas in the fully sequenced genome of the HL-adapted strain MED4, only a single and free-standing cpeB gene occurs. This gene encodes a derived form of beta-phycoerythrin, the function of which has remained enigmatic so far. Here, an analysis of HL-adapted Prochlorococcus strains from different ocean provinces revealed the presence of a cpeB gene highly similar to that of MED4. To investigate whether the presence of particular phycoerythrin genes is a common characteristic of the LL- and HL-adapted ecotypes, primer sets targeting specific motifs in LL-cpeB and HL-cpeB were designed for polymerase chain reaction (PCR) analysis of Red Sea phytoplankton. A major PCR product for Prochlorococcus HL-cpeB was obtained from samples taken at 5-70 m depth and for LL-cpeB from 70-125 m. The high sensitivity of this approach allowed the detection of HL-cpeB down to 100 m and LL-cpeB as deep as 175 m. DNA sequence and phylogenetic analysis of 70 individual clones for HL-cpeB and of 68 clones for LL-cpeB revealed a monophyletic origin for the HL and LL sequences respectively. This study shows that cpeB sequences are suitable as very sensitive molecular markers for the study of natural populations of Prochlorococcus. The low sequence divergence of HL-cpeB among Prochlorococcus strains, which have been isolated from the Mediterranean Sea, the Arabian Sea and the Southern Pacific Ocean as well as in populations from the Red Sea, suggests the HL-cpeB gene to be conserved and its product to be functional in Prochlorococcus.

Amino Acid Sequence↗
PubMed2004

Cytonuclear genomic dissociation in African elephant species.

African forest and savanna elephants are distinct species separated by a hybrid zone. Because hybridization can affect the systematic and conservation status of populations, we examined gene flow between forest and savanna elephants at 21 African locations. We detected cytonuclear dissociation, indicative of different evolutionary histories for nuclear and mitochondrial genomes. Both paternally (n = 205 males) and biparentally (n = 2,123 X-chromosome segments) inherited gene sequences indicated that there was deep genetic separation between forest and savanna elephants. Yet in some savanna locales distant from present-day forest habitats, many individuals with savanna-specific nuclear genotypes carried maternally transmitted forest elephant mitochondrial DNA. This extreme cytonuclear dissociation implies that there were ancient episodes of hybridization between forest females and savanna males, which are larger and reproductively dominant to forest or hybrid males. Recurrent backcrossing of female hybrids to savanna bulls replaced the forest nuclear genome. The persistence of residual forest elephant mitochondria in savanna elephant herds renders evolutionary interpretations based on mitochondrial DNA alone misleading and preserves a genomic record of ancient habitat changes.

Africa South of the Sahara↗
PubMed2026

Mutation timing, accumulation, and selection in the male germline shape inheritance risk for developmental disorders.

De novo mutations (DNMs) in the paternal germline are a major cause of developmental disorders, but how mutation timing, paternal age, and spermatogonial selection jointly shape transmissible risk within individual fathers is unclear. We combined trio whole-genome sequencing from 167 families with deep targeted NanoSeq profiling of sperm from 127 fathers of children with confirmed pathogenic DNMs. Transmitted DNM burden and paternal sperm mutation burden, spectra, and selection landscape were indistinguishable from population reference cohorts. Six fathers carried pathogenic early mosaic variants detectable in sperm at variant allele fractions (VAFs) of 0.7%-14.8%, creating individual recurrence-risk outliers. However, early mosaics accounted for ∼8% of the cohort-aggregated pathogenic burden exome-wide, compared with ∼18% from known positively selected drivers and ∼74% from other rare variants accumulating with paternal age. Thus, paternal de novo disease risk is shaped primarily by universal age-associated mutation and selection, while early mosaicism creates uncommon but clinically important high-risk individuals.

DNMs↗
PubMed1996

A novel G/A and the 4G/5G polymorphism within the promoter of the plasminogen activator inhibitor-1 gene in patients with deep vein thrombosis.

Plasma plasminogen activator inhibitor-1 (PAI-1) level was observed to be associated with sequence variations at the PAI-1 locus. Therefore, PAI-1 gene promoter was screened for possibly new polymorphisms and to investigate the contribution of these sequence variations to PAI-1 levels in patients with deep vein thrombosis (DVT). DNA was isolated from blood of 83 consecutive unrelated patients (42 +/- 11 years old) and from 50 apparently healthy subjects of similar age and gender distribution. Six fragments covering DNA sequence- 1523 base pairs (bp) upstream from the start of PAI-1 gene transcription to +90 bp in the first exon, were amplified by polymerase chain reaction and analyzed by single-strand conformation polymorphisms. Two polymorphisms were found: a previously described 4G/5G deletion/insertion polymorphism -675bp upstream from the start of transcription and a novel G/A single base substitution polymorphism further upstream at -844 bp. The two polymorphisms were in strong linkage disequilibrium. Significant differences between patients and controls were observed neither for the frequencies of the 4G/5G alleles (0.60/0.40 and 0.59/0.41, respectively) nor for the frequencies of the G/A alleles (0.33/0.67 and 0.41/0.59, respectively). The distribution of both polymorphisms was similar in idiopathic and secondary DVT as well as in first and recurrent DVT. In patients association between the 4G/5G genotypes and PAI activity was observed, with the highest values in the 4G/4G genotype (13.3 U/mL), median values in the 4G/5G genotype (9.8 U/mL) and the lowest values in the 5G/5G genotype (2.0 U/mL). Despite the lack of association between the G/A genotypes and plasma PAI-1 levels, electrophoretic mobility shift assay showed specific binding of a nuclear protein from human vascular endothelial cells extracts to both the G and the A variant, suggesting functional importance of this novel G/A polymorphism in regulating the expression of PAI-1 gene.

Adult↗
PubMed2000

Adaptive evolution of the African and Indonesian coelacanths to deep-sea environments.

We have PCR amplified and sequenced the rhodopsin (RH1) and evolutionarily closely related RH2 genes of the Indonesian coelacanth, now referred to as Latimeria menadoensis. When the RH1 and RH2 coding sequences are constructed, expressed in cultured cells, and reconstituted with 11-cis-retinal, the resulting visual pigments have wavelengths of maximal absorption (lambda(max)) of 485 and 479 nm, respectively. These lambda(max) values are identical to those of the African coelacanth, Latimeria chalumnae, showing that the Indonesian coelacanths also detect a narrow range of color. Statistical analyses show that the adaptation of the coelacanths toward the deep-sea started as early as 200 million years ago.

Adaptation, Physiological↗
PubMed2003

Filamentous "Epsilonproteobacteria" dominate microbial mats from sulfidic cave springs.

Hydrogen sulfide-rich groundwater discharges from springs into Lower Kane Cave, Wyoming, where microbial mats dominated by filamentous morphotypes are found. The full-cycle rRNA approach, including 16S rRNA gene retrieval and fluorescence in situ hybridization (FISH), was used to identify these filaments. The majority of the obtained 16S rRNA gene clones from the mats were affiliated with the "Epsilonproteobacteria" and formed two distinct clusters, designated LKC group I and LKC group II, within this class. Group I was closely related to uncultured environmental clones from petroleum-contaminated groundwater, sulfidic springs, and sulfidic caves (97 to 99% sequence similarity), while group II formed a novel clade moderately related to deep-sea hydrothermal vent symbionts (90 to 94% sequence similarity). FISH with newly designed probes for both groups specifically stained filamentous bacteria within the mats. FISH-based quantification of the two filament groups in six different microbial mat samples from Lower Kane Cave showed that LKC group II dominated five of the six mat communities. This study further expands our perceptions of the diversity and geographic distribution of "Epsilonproteobacteria" in extreme environments and demonstrates their biogeochemical importance in subterranean ecosystems.

Base Sequence↗
PubMed1994

Viral cell recognition and entry.

Rhinovirus infection is initiated by the recognition of a specific cell-surface receptor. The major group of rhinovirus serotypes attach to intercellular adhesion molecule-1 (ICAM-1). The attachment process initiates a series of conformational changes resulting in the loss of genomic RNA from the virion. X-ray crystallography and sequence comparisons suggested that a deep crevice or canyon is the site on the virus recognized by the cellular receptor molecule. This has now been verified by electron microscopy of human rhinovirus 14 (HRV14) and HRV16 complexed with a soluble component of ICAM-1. A hydrophobic pocket underneath the canyon is the site of binding of various hydrophobic drug compounds that can inhibit attachment and uncoating. This pocket is also associated with an unidentified, possibly cellular in origin, "pocket factor." The pocket factor binding site overlaps the binding site of the receptor. It is suggested that competition between the pocket factor and receptor regulates the conformational changes required for the initiation of the entry of the genomic RNA into the cell.

Intercellular Adhesion Molecule-1↗
PubMed2005

Partial release of the superficial medial collateral ligament for open-wedge high tibial osteotomy. A human cadaver study evaluating medial joint opening by stress radiography.

To perform an open-wedge high-tibial osteotomy (HTO), the medial proximal tibia is frequently exposed by partial distal release of the overlying insertion of the medial collateral ligament (MCL). Biomechanically, any release of the MCL can increase knee laxity when valgus stress is applied. Clinically however, post-surgical valgus instability following HTO with partial MCL release is an uncommon complication. It is known that the open-wedge procedure can re-tention an intact MCL by the width of the base of the wedge. However, this re-tentioning effect is uncertain in small wedge sizes, preexisting medial compartment laxity and in the presence of a partially detached MCL. Considering the good clinical results after HTO, we hypothesized that a partial release of the superficial MCL for HTO does not play a crucial role in stabilizing valgus forces in the human knee. We therefore measured the effect of partial versus complete release of the superficial MCL to determine medial knee laxity represented by the amount of medial joint opening (MJO) under valgus stress in this human cadaver study. In ten knee pairs, the superficial and deep MCL were sectioned in sequence with a standardized abduction force of 15 kp with a Scheuba apparatus applied. In group 1 (5 knee pairs), the superficial MCL was completely sectioned whereas in group 2 (5 knee pairs), sectioning of the superficial MCL was restricted to the anterior border to mimic the surgical exposure for an HTO. To account for the interindividual variability of ligamentous laxity, only increments of MJO within knee pairs were statistically evaluated. Stress radiography did not reveal any significant differences in increments of MJO between knee pair specimens with complete versus partial release of the superficial MCL. We disproved our hypothesis and concluded that the anterior fibers of the superficial MCL do play a crucial role in maintaining valgus stability in this biomechanical setting. Therefore, the release of the superficial MCL for open-wedge HTO should be kept to a minimum to decrease the potential of late valgus instability. This is especially important in patients with small wedge sizes and medial compartment laxity since the anterior MCL fibers are the main contributor to medial joint stability and the re-tentioning effect of the remaining MCL fibers is presumably decreased.

Adult↗
PubMed2025

Combined somatic mutation and transcriptome analysis reveals region-specific differences in clonal architecture in human cortex.

The human cerebral cortex is specialized into regions, but little is known about how human cellular lineages shape cortical regional variation and neuronal cell-type distribution during development. Here, we map single-cell lineages of human cortical regions and neuronal subtypes using >1,000 somatic single-nucleotide variants (sSNVs) identified from deep bulk whole-genome sequencing and analyzed over 25 regions and >72,000 single cells. In the fronto-parietal cortex, sSNVs are rarely restricted, marking neuron-generating clones that disperse into neighboring regions. In contrast, the primary visual cortex harbors 30%-70% more sSNVs than the neighboring secondary visual cortex. Clones at this border exhibit more restricted dispersion, suggesting late developmental lineage segregation. Single-nucleus sSNV and whole-transcriptome analysis reveal glutamatergic neuron clones with modest regional restrictions that share low-mosaic sSNVs with some GABAergic neurons, suggesting a recent dorsal cortical progenitor. Our analysis reveals human-specific cortical lineage patterns, regional differences in clonal patterns, and late divergence of some glutamatergic/GABAergic lineages.

Humans↗
PubMed1999

Phylogeny and diversity of Achromatium oxaliferum.

Achromatium oxaliferum was first described in 1893 by Schewiakoff as an unusually large bacterium living in freshwater sediments. Up to now no pure culture is available. Physical enrichments of achromatia collected from the acidic Lake Fuchskuhle, which houses a peculiar, smaller variety, and the neutral Lake Stechlin were investigated by the cultivation-independent rRNA approach. PCR in combination with cloning and sequencing was used for the retrieval of 24 partial and 4 nearly full-length 16S rRNA sequences that formed two distinct phylogenetic clusters. Fluorescence-in-situ-hybridization (FISH) with four 16S rRNA-targeted oligonucleotide probes unambiguously assigned the different sequences to either regular, large A. oxaliferum cells or to the smaller Lake Fuchskuhle population, tentatively named "A. minus". The two Achromatium sp. 16S rRNA sequence clusters form a stable deep branch in the gamma subclass of the class Proteobacteria. The closest cultivated relatives are Chromatium vinosum, Rhabdochromatium marinum and Ectothiorhodospira halophila with 16S rRNA similarities of 86.2 to 90.5%. Profound differences in the population structure of achromatia were revealed in the two lakes by FISH. In one sample from Lake Stechlin three genotypes could be visualized, and 49% of the cells were assigned to A. oxaliferum clone AST01, 28% to Achromatium sp. genotype AFK192/AFK433 and 23% to Achromatium sp. genotype AFK192/AST433. In contrast, a morphologically and phylogenetically homogeneous population of "A. minus". was present in Lake Fuchskuhle.

DNA, Ribosomal↗
PubMed2026

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.

RNA splicing shapes neuronal identity and disease risk, yet current maps lack the developmental resolution and depth to resolve this complexity. Here, we integrate deep long-read RNA sequencing and proteomics in induced pluripotent stem cell-derived cortical neurons to generate a high-resolution proteogenomic atlas of human neuron development. We identify 182,371 mRNA isoforms (over half previously unknown) and provide direct peptide evidence for the translation of hundreds of novel protein-coding sequences. Population genetics demonstrates that variants affecting novel exons and splice sites are under negative selection, underscoring the potential significance of these isoforms. During neuronal maturation, we observe that autism risk genes undergo dynamic isoform switching, including microexon inclusion and intron retention, that remodel key protein domains and regulatory regions. Furthermore, we uncover widespread, long-range coordination between alternative transcript processing events, including transcription start sites, exon splicing, and polyadenylation. Finally, our atlas enables variant reinterpretation in autism, highlighting the value of an isoform-centric view for interpreting pathogenic variation in neurodevelopment.

Humans↗
PubMed1988

Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat.

1. Pyramidal neurones from layers II and III of the rat primary somatosensory cortex and cat primary visual cortex were studied in vitro. Inhibitory postsynaptic potentials (IPSPs) and responses to exogenously applied gamma-aminobutyric acid (GABA) and its analogue baclofen were characterized. The results from rats and cats were very similar. 2. Single electrical stimuli to deep cortical layers evoked a sequence of PSPs in the resting neurone: (a) an initial, brief excitation (EPSP), (b) a short-latency, fast inhibition (the f-IPSP) and (c) a long-latency, more prolonged inhibition (the l-IPSP). The f-IPSP was accompanied by a large conductance increase (about 70-90 nS) and reversed polarity at -75 mV; the l-IPSP displayed a relatively small conductance increase (about 10-20 nS) and reversed at greater than -90 mV. 3. Focal application of GABA near the soma evoked a triphasic response when measured near the threshold voltage for action potentials: (a) the GABAhf (hyperpolarizing, fast) phase was very brief and was generated by a large conductance increase with a reversal potential of -78 mV, (b) the GABAd (depolarizing) phase also had a high conductance but reversed at -51 mV, (c) the GABAhl (hyperpolarizing, long-lasting) phase had a relatively low conductance and reversed at -70 mV. The GABAhf response was specifically localized to the soma, whereas the apical or basilar dendrites generated predominantly GABAd responses. 4. Baclofen, a selective GABAB receptor agonist, caused a small (about 2 mV), slow hyperpolarization of the resting potential, which reversed at -90 mV. Saturating baclofen doses increased membrane conductance by a maximum of about 12 nS. Baclofen depressed the amplitude and conductance of PSPs; when baclofen was focally applied near the soma. IPSPs were selectively depressed. 5. The GABAA receptor antagonists bicuculline methiodide or picrotoxin (10 microM) greatly depressed f-IPSPs, but either enhanced or did not affect l-IPSPs. Concomitantly, GABAhf and GABAd responses were antagonized, leaving a more prominent GABAhl response that reversed polarity at a more negative level of -87 mV. Baclofen responses were unaffected by bicuculline and picrotoxin. Extracellular barium abolished the baclofen response, and shifted the reversal potentials of the GABAd and GABAhl responses in the positive direction; the GABAhf response was unaffected. 6. Both focal GABA and f-IPSPs strongly depressed the intrinsic excitability of pyramidal neurones. Each greatly increased spike threshold and abolished or vastly reduced the capacity of the cells to fire repetitively during intense stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed2006

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: an imaging mimic of multiple sclerosis. A report of two cases.

OBJECTIVE AND IMPORTANCE: To describe the imaging findings of two cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mimicking multiple sclerosis. CLINICAL PRESENTATION AND INTERVENTION: Two cases presenting with neurological signs and symptoms were referred for magnetic resonance imaging (MRI) evaluation of the brain. Case 1 was a 36-year-old female patient presenting with recurrent headaches and recent onset numbness in the fingers of the right hand. Neurological examination showed a mild sensory deficit in the right hand. Case 2 was a 31-year-old female patient presenting with attacks of right-sided numbness of the face and body. The neurological examination revealed a sensory loss in the face and brisk deep tendon reflexes. Routine MRI sequences showed two types of lesions in both cases: 'punctate' hyperintense lesions on T(2)-weighted images (T(2)WI)/fluid-attenuated inversion recovery (FLAIR) images, hypointense on T(1)-weighted images (T(1)WI) and 'diffuse' white matter lesions, hyperintense on T(2)WI/FLAIR sequences and isointense to hypointense on T(1)WI. All lesions showed no contrast enhancement. Both cases were previously clinically and radiologically diagnosed as multiple sclerosis. There was a strong family history consistent with recurrent infarctions in other family members of both patients. Both cases were later diagnosed as CADASIL by skin biopsy/genetic linkage studies and follow-up. CONCLUSION: The cases showed that CADASIL causes stroke-like episodes in adults and can mimic multiple sclerosis on imaging. Clinical evaluation and MRI findings allow a differentiation of the two entities.

Adult↗
PubMed2000

[Arterial reoperation of the aorto-femoral segment].

Late rethromboses of aortofemoral prostheses following arterial reconstructions for aortoiliac occlusive disease (AIOD) are among the serious challenges faced by vascular surgeons. Hyperplasia of the intima, progressive atherosclerotic process, as well as regional hemodynamics impairment are taken to be the major factors promoting late rethrombosis development after arterial bypass for AIOD. It is the purpose of the study to assay the underlying causes and terms of rethrombosis in aortofemoral bypasses for AIOD, and analyze the results of the arterial reoperation procedures used. Over the period 1990-1997, 408 aortofemoral bypass procedures are performed in the University Hospital "St Catherine", with rethrombosis of the prostheses occurring in 19.45 per cent of the branches within 5 years of the initial intervention. Five methods of reoperation are used, with optimal results--100 per cent patency of prostheses--attained in aortobifemoral re-bypasses. Nevertheless, this particular operative procedure is considered as practicable in isolated, properly selected, relatively young patients free of associated diseases. In adults or patients with health problems preference is given to rather simple procedures, if possible performed under regional anesthesia, such as thrombectomy of the prosthesis (TE) using a deep femoral artery patch and/or sequence distal bypass towards arteria poplitea. The latter method accounts for limb salvage in 97.14 per cent of cases. A satisfactory outcome (88.58% preserved limbs) is likewise secured by resection of the failing distal anastomosis, and its substitution for neobifurcation towards the unobstructed AFS and APF. In elder and/or poor health patients the application of cross-over and axillofemoral bypasses are also advisable.

Adult↗
PubMed2004

Acute disseminated encephalomyelitis: a report of six cases.

Six children with Acute Disseminated Encephalomyelitis (ADEM) were seen at the Penang Hospital over a two year period (July 1999-June 2001). Diagnosis was based upon typical clinical features and characteristic findings on neuroimaging. Cerebrospinal fluid examination and other investigations were done, where appropriate, to rule out other causes of central nervous system disease. Three children had a prodromal illness. The most common presenting symptoms were fever, seizures, ataxia, focal neurological deficits and labile mood. Two children presented with status epilepticus. All children had an abnormal neurological examination. Brain magnetic resonance imaging revealed hyperintense signals on T2-weighted and FLAIR sequences in the subcortical and deep white matter regions of the frontal, parietal, and temporal lobes, as well as in the thalami, cerebellum and brainstem. One child had multiphasic disseminated encephalomyelitis (three episodes). The child with multiphasic disease had only one treated episode, and has suffered mild disability. Three children were treated with either methylprednisolone or immunoglobulins, and remain well. One child received both treatments but expired as a result of severe gastrointestinal bleeding from the use of methylprednisolone. The child who was not treated has severe disability.

Brain↗
PubMed1994

[Physiopathology of post-thrombotic syndrome. Update 1994].

The complex physiopathology of the post-thrombotic syndrome following deep venous thrombophlebitis involves a sequence of hemodynamic and biochemical events; development of the clinical picture, which remains susceptible to change, is a late occurrence following a long free interval. Despite re-establishment of venous patency, residual valvular lesions can cause orthostatic reflux. While residual occlusion generally has few long term repercussions, failure of the calf muscle venous pump is a serious potential consequence of such reflux. The clinical picture is less severe when the popliteal vein valves are not destroyed. The responsibility of wall compliance alterations has been proved as well. The initial thrombosis and/or the reflux may lead to associated incompetency of the perforating veins, then of the superficial venous network, thus aggravating the hemodynamic disturbances. The increased venous pressure results in alterations in upstream circulation, especially in the venous capillaries; the resultant increase in intraluminal pressure reduces fluid reabsorption. Edema remains intermittent so long as the lymphatic network withstands the excess workload. Thereafter, post-thrombotic lymphedema develops; the accompanying tissue fibrosis, a classical feature of the clinical picture, is attributed to the elevated concentration of macromolecules. This stage corresponds to lipo-dermato-sclerosis. The increase in the fibrinogen concentration, the reduction in tissue fibrinolytic activity, and the formation of pericapillary fibrin cuffs have all been considered as possible causes of leg ulceration. In fact, the assumed phenomenon of secondary hypoxia has not been demonstrated, and the fibrin cuffs do not appear to constitute a true barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamics↗
PubMed1997

Cortical and subcortical T2 shortening in multiple sclerosis.

Low signal intensity on long-repetition-time MR sequences has been observed in deep gray matter structures in patients with multiple sclerosis. This T2 shortening most likely represents a nonspecific degenerative process. We recently observed T2 shortening in the pericentral cortical gray matter and subcortical white matter in a patient with severe multiple sclerosis and we postulate that this represents an additional manifestation of neural degeneration.

Adult↗
PubMed1998

A novel mutation of Arg306 of factor V gene in Hong Kong Chinese.

We have analyzed 83 unrelated Hong Kong Chinese for the presence of genetic variants of factor V gene. Forty-three of them had a history of deep vein thrombosis. The DNA sequence variations of exons 7, 10, and 13, where the codons for Arg306, Arg506, and Arg679 are located, respectively, were studied by denaturing gradient gel electrophoresis. The G1691-->A (Arg 506-->Gln) mutation in exon 10 was not detectable in any of the 83 subjects. However, a high allelic frequency for the G1628-->A (Arg 485-->Lys) substitution was detectable in the same exon. We have also identified a novel DNA sequence mutation (A1090-->G) in exon 7 that resulted in Arg 306-->Gly substitution in 2 thrombotic patients and 1 nonthrombotic subject. Fresh blood samples were available from one of them for analysis of activated protein C resistance and the result was negative. Variation of DNA sequence was not found in exon 13 in any of our 83 subjects. The results of this study showed that, although the Arg 506-->Gln mutation was rarely found in the Hong Kong Chinese population, a different mutation site such as A 1090-->G in exon 7 of the factor V gene (Arg 306) may be of clinical importance.

Arginine↗