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Biomedical subjects

D Schindler

Publications and source records attributed to D Schindler.

101 records · Page 6Linked to original sources
PubMed1976

Mapping of trichodermin resistance in Saccharomyces cerevisiae: a genetic locus for a component of the 60S ribsomal subunit.

Resistance to the protein synthesis inhibitor trichodermin in Saccharomyces cerevisiae has been studied. A single recessive nuclear gene was responsible for resistance. The resistance locus, tcm1 was found to be closely linked (1 centi-morgan) to the locus pet 17 on the right arm of chromosome XV. The mutation to trichodermin resistance conferred resistance to other 12,13-epoxytrichothecenes and to the structurally unrelated antibiotic anisomycin.

Anisomycin↗
PubMedDate not supplied

Localisation of a Fanconi anaemia gene to chromosome 9p.

Using homozygosity mapping in a large consanguineous family, we have localised to chromosome 9p a further gene for the autosomal recessive, genetically heterogeneous disease Fanconi anaemia (FA). This is the fourth of at least eight FA genes to be localised to a discrete chromosomal region. Previously localised genes are FAA, FAC and FAD. By analysis of assigned families we show that the gene localised to chromosome 9p is FAF, FAG or FAH, or a new FA gene, and refine the localisation to the 21 cM region between markers D9S1678 and D9S175.

Chromosome Mapping↗
PubMedDate not supplied

A heterozygous frameshift mutation in the Fanconi anemia C gene in familial T-ALL and secondary malignancy.

BACKGROUND: Patients with Fanconi Anemia (FANC) have a well documented increased risk to develop malignancies, especially Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). The risk for heterozygous individuals is not clear, epidemiological data are inconsistent. If the risk for heterozygous individuals to develop malignancies was increased, they should be found in groups of patients with AML or MDS at higher proportion than in the normal population. We are currently screening a pediatric population with hematologic malignancies for mutations in the FANCA, FANCC and FANCG gene, and report here on siblings carrying a heterozygous frameshift mutation in the FANCC Gene. PATIENTS AND METHODS: Using PCR based single strand conformational analysis we screened the DNA from pediatric patients suffering from 1 degree or 2 degrees MDS, CMML/JMML or AML for mutations in the FANCA (43 exons), FANCC (14 exons) and FANCG (14 exons) gene, and included one patient with refractory T-ALL, being the brother of a patient with T-ALL and MDS transforming into AML. Aberrant PCR products were directly sequenced. Flowcytometric measurement of mitogen-sensitivity and G2-phase arrest is used to evaluate cultured stimulated lymphocytes from individuals carrying FANC-mutations. RESULTS: A novel heterozygous frame-shift mutation, 377-378delGA in the FANCC gene was found in 2 siblings, both suffering from T-ALL with subsequent MDS transforming to AML in one of them. No other mutation was found by direct sequencing of the complete FANCC gene. Both patients died under therapy. The parents (first degree cousins) and one healthy brother are also carriers. Their lymphocytes show a higher mutagen sensitivity than normal, but do not get blocked in G2 phase as being typical for Fanconi Anemia. CONCLUSION: As the mutation causes a premature Stopcodon within exon 4 of the FANCC gene it has to be regarded as a causal FANCC gene defect. The findings within this family support the hypothesis of an increased risk to develop malignancies in heterozygous carriers of FANC-mutations. A systematic screening of further patients is needed, and we are currently examining a larger cohort to get a better estimate of the true risk of heterozygosity.

DNA Mutational Analysis↗
PubMedDate not supplied

[Holoprosencephaly--clinical picture and genetic counseling in 6 cases].

Inadequate midfacial and forebrain development may result from constitutional chromosome aberrations, gene defects and, possibly, from as yet unidentified terato-genetic agents. The spectrum of clinical manifestations ranges from cyclopia with grossly incomplete organogenesis of the forebrain to apparently minor deviation from normal midface morphogenesis presenting as hypotelorism or absence of the philtrum. Such minor facial dysmorphias may, however, be likewise accompanied by severe anomaly in brain development and function. We report six cases of holoprosencephaly defects in children without demonstrable chromosomal anomalies. The presenting clinical symptoms in these cases were anomalies of cranio-facial shape, hypotelorism; nasal and ocular malformations, as well as median clefts. Some cases presented additional defects in extra craniofacial regions. Two infants who survived for several hours showed evidence of forebrain defects on CT-scans. Three of the cases suggest autosomal-recessive inheritance with 25% recurrence risk on the basis of proven or highly probable parental consanguinity. The remaining, presumably sporadic cases carry a low empirical recurrence risk. Three of the six cases received direct or indirect hormone treatments during early pregnancy.

Abnormalities, Multiple↗
PubMedDate not supplied

[Indication status of chromosome analysis in the diagnostic evaluation of recurrent abortions].

Parental (balanced) chromosome anomalies are one possible cause for the recurrence of miscarriages in the first three months of pregnancy. The preparation of karyotypes of the patients is thus an integral part of diagnostic clarification, yet the question of the relative importance of this examination among the range of diagnostic possibilities is the subject of controversy. This article reports on 112 couples examined cytogenetically over a period of four years as a result of recurrent miscarriages. In 6 cases (5.4%), chromosome aberrations were established that can be regarded as the cause of the recurrent miscarriages. With regard both to the examinations reported here and to the results published in recent literature, chromosome analysis of both partners is recommended after the second miscarriage as part of the first diagnostic steps taken.

Abortion, Habitual↗