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S Bundey

Publications and source records attributed to S Bundey.

At least 19 recordsLinked to original sources
PubMed2003

Eicosanoid involvement in the regulation of behavioral fever in the desert locust, Schistocerca gregaria.

The desert locust Schistocerca gregaria behaviorally thermoregulates in order to try and maintain a favoured "set point" body temperature. Locusts infected with the deuteromycete fungal pathogen Metarhizium anisopliae var acridumchoose a significantly elevated temperature. This "behavioral fever" greatly delays the progress of mycosis. We have confirmed this phenomenon and shown that desert locusts also fever when infected with the bacterial pathogen Serratia marcescens. Elevation in the prefered environmental temperature occurs also upon injection with laminarin and lipopolysaccharide (microbial cell wall components). Since such treatments also stimulate the immune system it would appear that "behavioral fever" is probably a feature of the immune response. The eicosanoid biosynthesis inhibitor dexamethasone prevented laminarin invoked fever. This effect was reversable by arachidonic acid. Therefore in common with the febrile response in mammals behavioral fever in insects may be mediated locally by circulating eicosanoids.

Animals↗
PubMed1999

A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25.

Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied were identified from databases of patients in different regions of the United Kingdom. After ascertainment and clinical assessment, we performed a genomewide search for linkage, using 290 polymorphic DNA markers. In three families, a region of homozygosity at chromosome 2q24-q25 was identified between the markers D2S124 and D2S148. The largest family gave a maximum LOD score of 3.0, by multipoint analysis (HOMOZ). The maximum combined multipoint LOD score for the three families was 5.75. The minimum region of homozygosity is approximately 5 cM between the markers D2S124 and D2S2284. We have shown that a proportion of autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. The identification of genes involved in the etiology of cerebral palsy may lead to improved management of this clinically intractable condition.

Adolescent↗
PubMed1998

A comparison of disease and gene frequencies of inborn errors of metabolism among different ethnic groups in the West Midlands, UK.

OBJECTIVE: To assess birth and gene frequencies of specific autosomal recessively inborn errors of metabolism (IEM) within different ethnic groups. DESIGN: Retrospective study in a regional centre for investigation and treatment of IEM. SUBJECTS: All children born within the West Midlands NHS Region, UK, during the decade immediately preceding the 1991 National Census. METHODS: Birth frequencies for individual IEM were calculated separately for the main ethnic groups in the West Midlands using data from the West Midlands Neonatal Screening Programme, the regional register of IEM patients, and population frequencies from the National Census. Gene frequencies were calculated using previously documented observations on parental consanguinity rates and inbreeding coefficients. RESULTS: The overall incidence of recorded IEM was tenfold higher among Pakistanis compared to white children (1:318 v 1:3760), whereas only one AfroCaribbean child was identified (incidence 1:16 887). Tyrosinaemia type 1, cystinosis, mucopolysaccharidosis type 1, non-ketotic hyperglycinaemia, and hyperchylomicronaemia all occurred more frequently among Pakistanis. An increased gene frequency was only confirmed for tyrosinaemia. The incidence of phenylketonuria was similar in Pakistani and white children (1:14 452 v 1:12 611), but the gene frequency was significantly lower in Pakistanis (1:713 v 1:112). These results illustrate the interplay between gene frequency and parental consanguinity in determining disease frequencies in different populations, and indicate anticipated disease frequencies in the absence of consanguineous marriage. These figures have implications for the organisation of services for management of inborn errors, for genetic counselling, and for the assessment of gene flow in world populations.

Ethnicity↗
PubMed1997

A novel mechanism of aberrant pre-mRNA splicing in humans.

Eukaryotic pre-mRNA splicing is regulated by consensus sequences at the intron boundaries and branch site. Recently, Sirand-Pugnet et al. reported the importance of an additional intronic sequence, an (A/U)GGG repeat in chicken beta-tropomyosin that is a binding site for a protein required for spliceosome assembly. Interestingly, we have detected mutations in IVS3 of the human growth hormone (GH) gene that affect a putative, homologous consensus sequence and which also perturb splicing. In a series of dominant-negative GH mutations that cause exon skipping, we found two mutations that do not occur within the 5' and 3' splice sites, or branch consensus sites. The first mutation is a G-->A transition of the 28th base (+28G-->A) of and the second deletes 18 bp (del+28-45) of IVS3 of the human GH gene. These mutations segregated with autosomal dominant GH deficiency in both kindreds and no other allelic GH gene changes were detected. RT-PCR amplification of transcripts from expression vectors containing the +28G-->A or del+28-45 alleles yielded products showing a >10-fold preferred use of alternative splicing, similar to findings previously reported for IVS3 donor site mutations. Both mutations are located 28 bp downstream from the 5' splice site and examination of the sequences perturbed revealed an intronic XGGG repeat similar to the repeat found to regulate mRNA splicing in chicken beta-tropomyosin. Interestingly, the XGGG repeats involved in our mutations exhibit homologous spacing to those in a so-called 'winner' RNA sequence. Binding of A1 heterogeneous nuclear ribonucleoprotein (hnRNP) by 'winner' sequences in pre-mRNA transcripts is thought to play an important role in pre-mRNA packaging and transport as well as 5' splice site selection in pre-mRNAs that contain multiple 5' splice sites. Our findings suggest that (i) XGGG repeats may regulate alternative splicing in the human GH gene and (ii) mutations of these repeats cause GH deficiency by perturbing alternative splicing. Mutations of homologous intron sequences may underlie other human diseases.

Alleles↗
PubMed1997

Symmetry of neurological signs in Pakistani patients with probable inherited spastic cerebral palsy.

Seven Pakistani families are described with children manifesting a spastic cerebral palsy-like syndrome. One feature common to all affected patients was symmetry of neurological signs. Only one of these families had been offered genetic counselling and fewer than half had undergone clinical investigations. The importance of symmetry of neurological signs is reaffirmed as an indicator of a probable genetic aetiology in children with spasticity. Many families at risk of recurrence are not offered appropriate genetic advice, and some children with potentially diagnosable conditions are given a label of cerebral palsy without investigation of possible underlying inherited disorders.

Age of Onset↗
PubMed1997

Usher syndrome in the city of Birmingham--prevalence and clinical classification.

AIMS: To estimate the prevalence of Usher syndrome in the city of Birmingham, and to establish a database of patients who have been classified into different clinical subtypes essential for future gene mutation analysis. METHODS: Symptomatic cases of Usher syndrome (US) resident in the city of Birmingham in June 1994 were ascertained through multiple sources. Ophthalmic and audiological reassessment together with examination of medical records and patient questionnaires allowed classification of three subtypes, US 1, US 2, and US 3. In addition, family pedigrees were examined and blood was taken from index patients for DNA extraction. RESULTS: In the population aged over 15 years the prevalence was 6.2 per 100 000 population for all US subtypes. The prevalence for US 1 and US 2 was 5.3 per 100 000 population. This is greater than previously reported. In the age group 30-49 years the prevalence approached 1 in 10 000. Clinical classification found 33% US 1, 47% US 2, and 20% US 3. CONCLUSION: This higher prevalence rate and greater frequency of US 2 and US 3 may reflect a more complete ascertainment.

Adolescent↗
PubMed1997

Fragile X syndrome is less common than previously estimated.

In 1986, a population study of school children in the city of Coventry gave an overall prevalence in males and females for fragile X syndrome of 1/952. The 29 children diagnosed as having fragile X syndrome in this study have been re-evaluated with molecular diagnostic techniques. Eighteen of the original 29 children have been found not to have the expansion of the FMR1 gene associated with fragile X syndrome. Revised prevalence figures have been calculated giving rise to an overall prevalence figure of 1/2720 (range 1/2198-1/3089). If the four children lost to follow up are also assumed not to have the fragile X syndrome, the revised prevalence figure was 1/5714 (range 1/4762-1/6349). Clinical review of boys with severe mental retardation from this and a subsidiary study show that the clinical features of head circumference greater than the 50th centile, testicular volume greater than the 50th centile, and IQ between 35 and 70 remain helpful in distinguishing boys with fragile X syndrome from those who have non-specific mental retardation.

Adolescent↗
PubMed1996

ERG and EOG abnormalities in carriers of X-linked retinitis pigmentosa.

The diagnosis of X-linked retinitis pigmentosa (XL-RP) relies on the identification of the female carriers, in whom fundal abnormalities are often minimal and variable. The electroretinogram (ERG) has been reported as abnormal in 54-96% of heterozygote females. This study examines the combined use of electro-oculogram (EOG) and standardised ERG in 31 obligate and 33 non-obligate carriers of XL-RP. In the obligate carrier group, the EOG was abnormal in 13 carriers (41%), the ERG abnormal in 21 carriers (68%) and a combined EOG and ERG abnormality occurred in 24 carriers (77%). An EOG abnormality alone occurred in 2 carriers (6.5%). Fourteen obligate carriers (45%) showed a peak to peak delay of the ERG scotopic b wave, this being a previously unreported phenomenon. Similarly, in the non-obligate carrier group, the EOG was abnormal in 11 carriers (44%) and the ERG abnormal in 19 carriers (73%). The results of this study suggest that the use of both tests, including measurement of the scotopic b wave latency, may increase the carrier detection rate.

Adolescent↗
PubMed1996

The representation of ethnic minorities at genetic clinics in Birmingham.

A study of the ethnic distribution of families attending genetic clinics in Birmingham has shown a deficit of Afro-Caribbean and Pakistani families. The former may be because of a deficiency of autosomal recessive diseases other than sickle cell disease, but the numbers are too small to be certain of this. The deficit of Pakistani families is probably for a variety of causes, such as a poorer attendance rate at clinics unless there is some encouragement, and a lack of awareness of, or interest in, genetic issues.

Adolescent↗
PubMed1996

Linkage of Wolfram syndrome to chromosome 4p16.1 and evidence for heterogeneity.

Wolfram syndrome (DIDMOAD syndrome; MIM 222300) is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and bilateral optic atrophy. Previous linkage analysis of multiply affected families indicated that the gene for Wolfram syndrome is on chromosome 4p, and it produced no evidence for locus heterogeneity. We have investigated 12 U.K. families with Wolfram syndrome, and we report confirmation of linkage to chromosome 4p, with a maximum two-point LOD score of 4.6 with DRD5, assuming homogeneity, and of 5.1, assuming heterogeneity. Overlapping multipoint analysis using six markers at a time produced definite evidence for locus heterogeneity: the maximum multipoint LOD score under homogeneity was <2, whereas when heterogeneity was allowed for an admixture a LOD of 6.2 was obtained in the interval between D4S432 and D4S431, with the peak close to the marker D4S3023. One family with an atypical phenotype was definitely unlinked to the region. Haplotype inspection of the remaining 11 families, which appear linked to chromosome 4p and had typical phenotypes, revealed crossover events during meiosis, which also placed the gene in the interval D4S432 and D4S431. In these families no recombinants were detected with the marker D4S3023, which maps within the same interval.

Adolescent↗
PubMed1994

Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism.

BACKGROUND: Type II (tyrosinase-positive) oculocutaneous albinism is an autosomal recessive disorder that has recently been mapped to chromosome segment 15q11-q13. The frequency of this disorder is greatly increased in patients with Prader-Willi or Angelman syndrome, both of which involve deletions of chromosome 15q. The P protein is a transmembrane polypeptide that may transport small molecules such as tyrosine, the precursor of melanin. The P gene is located in chromosome segment 15q11-q13. METHODS: We studied the tyrosinase and P genes in three patients with type II oculocutaneous albinism, one of whom also had Prader-Willi syndrome, and in one patient with a milder syndrome known as autosomal recessive ocular albinism. Individual exons of these genes were amplified from the DNA of each patient by the polymerase chain reaction and screened for mutations by simultaneous analyses of single-stranded conformation polymorphisms and heteroduplexes and subsequent DNA sequencing. RESULTS: Mutations of the P gene were identified in all four patients. These included one frame shift, three missense mutations that result in amino acid substitutions, and one mutation that affects RNA splicing. The patient with Prader-Willi syndrome plus albinism had a typical deletion of the paternal chromosome 15, rendering him hemizygous for a maternally inherited mutant allele of the P gene. The child with ocular albinism was heterozygous for two different mutations in the P gene. CONCLUSIONS: Abnormalities of the P gene are associated with a wide range of clinical phenotypes, including type II oculocutaneous albinism, albinism associated with the Prader-Willi syndrome, and at least some cases of autosomal recessive ocular albinism.

Albinism↗
PubMed1994

Duplication of the 15q11-13 region in a patient with autism, epilepsy and ataxia.

Various developmental abnormalities can give rise to the clinical syndrome of autism, and some are due to chromosomal anomalies. One syndrome has been identified in which behavioural disorder is associated with the clinical features of epilepsy and ataxia, and with the chromosomal anomaly of an extra marker chromosome containing a duplication of 15q11-13. The authors report a boy with autism, epilepsy, ataxia and an interstitial duplication of 15q, in whom molecular analysis reveals duplication of the GABRA5 and GABRB3 genes on the maternally derived chromosome.

Ataxia↗