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T Grimm

Publications and source records attributed to T Grimm.

At least 73 records · Page 4Linked to original sources
PubMed1991

A comparison of drug protein binding and alpha 1-acid glycoprotein concentration in Chinese and Caucasians.

alpha 1-acid glycoprotein (AAG) concentration and the binding of both lignocaine and warfarin were compared in 15 healthy Chinese and age and sex matched Irish (Caucasian) subjects. Both the extent of lignocaine binding and AAG concentrations were significantly (P less than 0.05) lower in Chinese subjects. No difference was shown in warfarin binding. These results suggest that the binding of basic drugs may be significantly less in Chinese than Caucasians, and lower concentrations of the binding protein AAG are a major determinant of this difference.

Adult↗
PubMed1991

Confirmation of linkage of hyperkalaemic periodic paralysis to chromosome 17.

Linkage studies were performed in six European families with hyperkalaemic periodic paralysis (PPII) with myotonia, an autosomal dominantly inherited disorder characterised by episodic weakness. The weakness is caused by non-inactivating sodium channels of reduced single channel conductance of the muscle fibre membrane. Recently, portions of the gene coding for the alpha subunit of the sodium channel of the adult human skeletal muscle (h-Na2) have been cloned and localised on chromosome 17q with no recombinants to the human growth hormone locus (GH1). Linkage between these two chromosome 17 markers and the disease was shown in our families (Z = 7.14, 0 = 0.00). These results, combined with the linkage data of a single large American family, suggest that the disease is caused by dominant mutations of the adult sodium channel, and that it is probably a genetically homogeneous disorder. Hyperkalaemic periodic paralysis is the first non-progressive myotonic disorder to be localised on the human genome.

Chromosomes, Human, Pair 17↗
PubMed1991

Evidence supporting tight linkage of X-linked Emery-Dreifuss muscular dystrophy to the factor VIII:C gene.

In a large German family with Emery-Dreifuss muscular dystrophy (EDMD) linkage analysis was performed using the factor IX gene (F9), the factor VIII:C gene (F8), the anonymous DNA probe DXS52, and DXS15 as markers. Tight linkage was found between the EDMD locus and the F8 probe (Zmax = 1.19; theta max = 0.00), DXS15 (Zmax = 1.75; theta max = 0.00) and DXS52 (Zmax = 2.26; theta max = 0.00). Weak linkage was found to F9 (Zmax = 0.02; theta max = 0.43). The data from the literature and our results suggest that the gene locus of EDMD is close to F8 (confidence interval theta = 0-0.07). The new linkage data are useful for carrier detection and diagnosis of EDMD patients before onset of major clinical signs.

Cardiomyopathies↗
PubMed1991

Genetic risks for children of women with myotonic dystrophy.

In genetic counseling, the recommended risk estimate that any heterozygous woman with myotonic dystrophy (DM) will have a congenitally affected child is 3%-9%. However, after already having had such an offspring, a DM mother's risk increases to 20%-37%. The risks of 10% and 41%, respectively, calculated in this study are similar to the estimates in the literature. However, our data on clinical status of the mothers demonstrate that only women with multisystem effects of the disorder at the time of pregnancy and delivery are likely to have congenitally affected offspring. No heterozygous woman with polychromatic lens changes but no other clinically detectable multisystem involvement had a congenitally affected child. In addition, our data suggest that the chance of having a more severely affected child increases with greater severity of maternal disease. The findings of this study are relevant for genetic counseling, as the risk of having a congenitally affected child for women with classical manifestations of the disease is shown to be higher than predicted by the overall risk estimate for any heterozygous woman. We consider it appropriate to give these classically affected women risk figures which approach the recurrence risk given to mothers with congenitally affected children. However, the risk of having a congenitally affected child for heterozygous women with no multisystem involvement appears to be minimal. Our findings support the earlier proposed hypothesis of maternal metabolites acting on a heterozygous offspring. Neither genomic imprinting nor mitochondrial inheritance is able to explain the correlation between the clinical status of heterozygous mothers and that of their children.

Adolescent↗
PubMed1990

Theoretical considerations on germline mosaicism in Duchenne muscular dystrophy.

A newly formulated mutation selection equilibrium for lethal X linked recessive traits such as Duchenne muscular dystrophy is presented, which allows for both male and female germline mosaicism. Estimates of the additional parameters used are given, thus allowing the incorporation of germline mosaicism into the calculation of genetic risks.

Female↗
PubMed1989

Problems in genetic counseling in a family with an "atypical" centronuclear myopathy.

Genetic counseling often deals with a rare disease the inheritance of which is not clearly established or in which genetic heterogeneity is reported. In addition, relevant parameters such as penetrance, gene frequency, and mutation rate may not be available. In this situation, establishing the risk may be very difficult. An example is presented in which Bayesian risk calculation proved to be of great help in providing precise risk estimates in a family in which an "atypical" centronuclear myopathy was segregating.

Adult↗
PubMed1989

Benign muscular dystrophy: risk calculation in families with consanguinity.

This report concerns two families in which the index patients are sporadic cases of a benign form of muscular dystrophy. In both families the sisters of the patients have married a close relative. The respective risks for a child of these consanguineous marriages being affected with either X linked Becker muscular dystrophy or autosomal recessive limb girdle muscular dystrophy is calculated using pedigree information, results of serum creatine kinase determinations, and also, in one family, results of DNA typing using RFLPs from the short arm of the X chromosome.

Bayes Theorem↗
PubMed1989

Hot spot of recombination within DXS164 in the Duchenne muscular dystrophy gene.

The DMD gene, which spans more than 2,000 kbp, has been assigned to band Xp21 of the X chromosome. Two subclones (PERT 87-1 and PERT 87-15) of the intragenic locus DXS164 physically are separated by approximately 60 kbp. Linkage studies were done in 49 informative DMD families by using the LINKAGE program. Crossing-over between the loci studied occurred in four families. A recombination rate of 4% (support interval [Zmax-1] 1%-10%), which was 54 (support interval 14-135-fold) times higher than expected, was found with a maximum lod score of 13.50. These data suggest a hot spot for recombination within DXS164.

Alleles↗
PubMed1988

Prenatal exclusion of Norrie disease with flanking DNA markers.

Three polymorphic DNA markers linked to the locus of Norrie disease were used for indirect genotype analysis in a ten-wk-old fetus at risk for the disease. When haplotypes of the family members and the estimated recombination frequency between Norrie gene and each of the DNA marker loci DXS7, DXS84, and DXS146 were taken into account, the risk that the fetus had inherited the mutation was about 1%.

Adult↗
PubMed1988

The human tyrosine aminotransferase gene: characterization of restriction fragment length polymorphisms and haplotype analysis in a family with tyrosinemia type II.

Deficiency in hepatic tyrosine aminotransferase (TAT) causes tyrosinemia type II, an autosomal recessively inherited disorder. Using a TAT cosmid clone, we have identified an MspI restriction fragment length polymorphism (RFLP) 5' to the TAT gene, with allele frequencies of 0.63 and 0.37. Analysis of the cloned maternal and paternal TAT alleles from a patient with tyrosinemia type II led to the identification of a HaeIII RFLP at the 3' end of the TAT gene, with allele frequencies of 0.94 and 0.06. The two RFLPs are 27 kb apart and in no allelic association. From haplotype frequencies, a polymorphism information content (PIC) value of 0.44 was obtained. The two RFLPs have allowed the unambiguous identification of the mutant TAT alleles in the patient's pedigree by haplotype analysis.

Amino Acid Metabolism, Inborn Errors↗
PubMed1987

A chromosome supplement to the London Dysmorphology Database.

A supplement to the computerised database for the diagnosis of rare dysmorphic syndromes described by Winter et al is presented, which includes a list of syndromes occurring in patients with unbalanced chromosome aberrations. The extension of the original programme is based on Schinzel's Catalogue of unbalanced chromosome aberrations in man.

Abnormalities, Multiple↗
PubMed1986

Estimation of the male to female ratio of mutation rates from the segregation of X-chromosomal DNA haplotypes in Duchenne muscular dystrophy families.

A novel procedure is presented to estimate the ratio of male to female mutation rates for Duchenne muscular dystrophy (DMD). X-specific restriction fragment length polymorphisms are used to establish DNA haplotypes in three-generation DMD families. From the proportion of DMD patients who have inherited their maternal grandfather's X chromosome, the ratio of mutation rates can be calculated. In contrast to classical methods, the proposed procedure is not restricted to sporadic or familiar cases nor is any information on the carrier status of female relatives required.

DNA↗
PubMed1986

Chromosome 7 short arm deletion, 7p21----pter.

A case report of a de novo deletion in the short arm of chromosome 7 is presented (46,XX,del(7)(p21----pter)). The five-month-old girl's major symptoms are: trigonocephalus with craniosynostosis, median bony forehead bulge, high palate, atrial septal defect, anal atresia and perineal fistula, thumb insertion far to ulnar-proximal, and a slightly retarded psychomotor development. The other cases with monosomy 7p described in the literature are reviewed.

Abnormalities, Multiple↗
PubMed1986

Peroneal somatosensory evoked potentials in the "pure" form of hereditary spastic paraplegia.

Two patients suffering from the stationary form of hereditary spastic paraplegia, father and son, are described. While in the father the disease - probably because of congenital clubfeet - led to flexion contractures of the hip- and knee-joints, the son in contrary showed extreme genua recurvata. In spite of these contradictionary findings, neurological examination of both patients led to the diagnosis of stationary form of hereditary spastic paraplegia. Both patients had normal latencies of their somatosensory evoked peroneal cortical potentials (Peron-SEP). It is known that the progredient form of the disease leads to alterations of the Peron-SEP. So it is the opinion of the authors that this electrodiagnostic aspect might allow to distinguish between the "pure" and the progredient form of the disease in less clear cases, if these findings can be confirmed in other sibships with the "pure" form of hereditary spastic paraplegia.

Adult↗
PubMed1986

Autosomal recessive or sex linked recessive: a counselling dilemma.

This paper discusses the difficult problem that arises when information is sought by female relatives of two or more brothers, each of whom has an identical but undiagnosed or 'new' syndrome, which is likely to be either autosomal recessive or sex linked recessive in inheritance. It is proposed that standard Bayesian methods may be applied in this situation thus incorporating the prior probability for each event with conditional probabilities based upon pedigree analysis.

Female↗