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Biomedical subjects

M S Newton

Publications and source records attributed to M S Newton.

At least 19 recordsLinked to original sources
PubMed1987

Ten families with fragile X syndrome: linkage relationships with four DNA probes from distal Xq.

We present clinical, cytogenetic, and linkage data of four DNA probes from the terminal long arm of the X chromosome in ten new families with fragile X syndrome. A prior/posterior method of multipoint linkage analysis is employed to combine these results with published data to refine the linkage map of terminal Xq. Ten possible probe/disease orderings were tested. The order with the greatest posterior probability (0.78) of the five loci is 52a-F9-fragile X gene-DX13-St14, although the order with reversal of the positions of 52a and F9 has a posterior probability 0.15. The mean estimates of the distances between the probes and the fragile X gene are 38 cM and 33 cM for the proximal probes 52a and F9, and 8 cM and 12 cM for the distal probes DX13 and St14. Although the current method of choice in the prenatal diagnosis and carrier detection of the fragile X syndrome remains detailed cytogenetic analysis, consideration is given to the potential role of these DNA probes, both singly and in pairs.

Chromosome Banding↗
PubMed1985

Forty four probands with an additional "marker" chromosome.

Information is presented which has been obtained from an exhaustive examination of 44 probands with a supernumerary marker chromosome (mar) and their families. The data include the derivation of the mar, frequency in various populations, inheritance and possible effect on fertility, congenital abnormality, and mental ability. The practical problems in assessing the risk of abnormality in a foetus discovered during prenatal diagnosis to be carrying a mar, are discussed.

Adult↗
PubMed1985

Molecular analysis of chromosome 11 deletions in aniridia-Wilms tumor syndrome.

We describe five individuals who have constitutional deletions of the short arm of one chromosome 11, including all or part of the band p13. All of these individuals suffer from aniridia; two have had a Wilms tumor removed. We have established lymphoblastoid cell lines from these and in three cases constructed somatic cell hybrids containing the deleted chromosome 11. Analysis of DNA from the cell lines and hybrids with a cloned cDNA probe has shown that the catalase gene is deleted in four of five patients. The catalase locus must be proximal to the Wilms and aniridia-related loci. We have not detected a deletion of the beta-globin or calcitonin genes in any of these individuals; we conclude these genes are likely to be outside the region 11p12-11p15.4. In addition, we have used monoclonal antibodies in fluorescence-activated cell sorting analysis to measure expression in the hybrids of two cell surface markers encoded by genes that map to the short arm of chromosome 11. The genes for both of these are deleted in two individuals but are present in the individual with the smallest deletion.

Antigens, Surface↗
PubMed1983

Mutagen hypersensitivity in Friedreich's ataxia.

Cultured blood lymphocytes from nine patients with Friedreich's ataxia (FrA) and nine matched controls were exposed to a series of graded doses of mitomycin C and ethyl methane sulphonate and examined for the incidence of sister chromatid exchange (SCE). The spontaneous SCE levels did not differ between patients and controls, but the cells from each of the patients showed a significantly enhanced response to the induction of SCE by both mutagens - the patients' cells being up to 50% more sensitive than controls. Cultures from five FrA patients and five controls were analysed to determine the spontaneous incidence of chromosomal aberrations and exposed to a graded series of X-ray doses to measure their response to radiation-induced chromosome damage. The spontaneous aberration incidence in controls did not differ from that found in other control series, but the background incidence of aberrations in cells from the FrA patients was significantly above control levels and appeared to reflect an enhanced response to diagnostic exposure to radionuclides. The FrA cells showed a significantly enhanced in vitro response to chromosome aberration induction by X-rays, the net aberration yields being some 60% greater than those in irradiated controls at doses up to 200 rads. It is concluded that FrA is yet another syndrome which shows hypersensitivity to the induction of chromosome damage by mutagens. Possible factors responsible for this hypersensitivity are discussed and comparisons drawn with ataxia telangiectasia, another autosomal recessive disease characterized by enhanced X-ray sensitivity.

Adult↗
PubMed1983

Spontaneous and mutagen induced sister chromatid exchange in multiple sclerosis.

Spontaneous and mutagen induced sister chromatid exchange (SCE) frequencies have been studied in nine patients with multiple sclerosis and in nine age and sex matched healthy controls. The incidence of spontaneous SCE in lymphocytes of the MS patients was significantly greater, by about 50%, than in those of the control subjects. When exposed to mitomycin C (MMC) or ethyl methane sulfonate (EMS) in vitro, cells from both groups showed typical dose dependent increases in SCE frequency, with yields from MS patients slightly higher than from controls. The higher SCE yields in mutagen treated MS cells relative to controls is considered to reflect initial basal differences between the cell types, so that MS cells are not intrinsically hypersensitive to mutagen treatment.

Adult↗
PubMed1982

The response of cells from patients with Huntington's chorea to mutagen-induced chromosome damage.

Cultured blood lymphocytes from 15 patients with Huntington's chorea (HC) and matched controls were exposed to a series of graded doses of mitomycin C and ethyl methane sulphonate and examined for the incidence of sister chromatid exchange (SCE). The spontaneous SCE levels did not differ between HC patients and controls and although cells from the majority of HC patients showed a slightly enhanced response to SCE induction by the mutagens, the enhancement was small and significant only on the pooled data. Cultures from 4 HC patients and controls were exposed to a graded series of X-ray exposures and no difference was observed in the spontaneous aberration frequencies between HC cells and controls, or in their response to aberration induction by X-rays. Skin fibroblast cultures derived from three HC patients, two xeroderma pigmentosum patients and two healthy controls were exposed to MMC and the levels of unscheduled DNA synthesis determined. There was no difference between the response of HC cells and normal controls, although such synthesis in the xeroderma cells was severely depressed. It is concluded that: (i) fibroblasts and lymphocytes from HC patients show a normal response to the three mutagens studied; (ii) there is no evidence for any defect in processes involved in repairing the lesions induced; (iii) the slightly elevated response of HC lymphocytes to SCE induction may reflect the presence of a different proportion of a slightly more sensitive T cell sub-set in HC patients, and (iv) HC cells do not show a hypersensitivity to mutagens that could be used as a basis for diagnosis.

Cells, Cultured↗
PubMed1981

Phenotypically normal individuals with an inversion (X) (p22q13) and the recombinant (X), dup q.

Two families are described in which there is an inv(X) (p22q13) which has been transmitted for three generations. In one family (K482), no recombinants have been recovered and the inversion can be traced to a female born in 1839. In the second family (K491), a recombinant (X), dup q, has been recovered in a normal fertile woman. In both families the inverted X appears to be carrying the Xg allele. Despite extensive family studies no common ancestor has been found for the two families. The pattern of DNA synthesis has been studied in those individuals who are karyotypically 46,X,inv(X) (p22q13) and 46,X,rec(X)dup 1, inv(X) (p22q13); the selection of the abnormal as the late synthesizing X chromosome is random in the former and total in the latter. In some cells the two long arms of the recombinant X chromosome showed asynchrony of DNA replication.

Adult↗
PubMed1980

Hypostatic leg ulceration and Klinefelter's syndrome.

Sixty-one patients with Klinefelter's syndrome, of both normal and low intelligence, have been found to have a significantly higher frequency of hypostatic leg ulceration than a random sample of normal males, a group of male prisoners and a group of mentally subnormal men. The prevalence of varicose veins in these patients is also greater than in normal men and in prisoners but not significantly different from that of the mentally subnormal group.

Adolescent↗
PubMed1975

Familial transmission of a (21q22q) translocation.

A large family is described in which a (21q22q) Robertsonian translocation is segregating through three generations. The assessment of the risk of a translocation carrier producing an offspring with Down's syndrome is calculated from the data in this family and eight others reported in the literature. The risk when the translocation carrier is a female is approximately 6 in 100, or 0.06. For the male translocation carrier the risk can only be guessed, since the patients with Down's syndrome born to these parents were probands. The risk for Down's syndrome from the combined data of male and female translocation carriers in 3 is 100, or 0.03.

Adolescent↗