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M Durner

Publications and source records attributed to M Durner.

24 records · Page 2Linked to original sources
PubMed1992

Is there a genetic relationship between epilepsy and birth defects?

Children of epileptic mothers have a greater risk for congenital malformations than is seen in the general population. This risk has been attributed mostly to teratogenic effects of antiepileptic drugs, but other risk factors have been suggested, such as epilepsy, per se, or some underlying genetic defects associated with epilepsy. Previous studies do not answer the question of whether genetic factors contribute to the high risk of malformations in children of epileptic parents. Genetic studies in families of patients with neural-tube defects and cleft lip (CL), with and without cleft palate (CP), as well as genetic studies in families of patients with epilepsy, show evidence for the possible existence of genes on the short arm of chromosome 6. The suspected gene for CL and CP is linked to factor XIIIa and is neither identical with or linked to a gene for idiopathic generalized epilepsy, which is close to the HLA region. The short arm of chromosome 6 also contains a human homologue of the mouse t-complex. Alterations of the mouse t-complex are involved in defects of neural-crest development in mice. Relationships between a human homologue of the mouse t-complex, epilepsy, and birth defects have yet to be proven.

Abnormalities, Drug-Induced↗
PubMed1991

Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6.

Juvenile myoclonic epilepsy (JME) is a generalized, non-progressive epilepsy characterized by an adolescent onset of sudden, involuntary myoclonic jerks. Greenberg et al. (American Journal of Medical Genetics 31:185-192, 1988b; Cytogenetics and Cell Genetics 51:1008, 1989b) reported tight linkage of a JME locus to the HLA region of chromosome 6p. We confirm this linkage assignment, although at a larger recombination fraction than previously reported. Twenty-three, mostly nuclear, families were ascertained through a JME proband. The affected status of relatives of the probands was assigned by 4 different clinical criteria, and separate analyses were done assuming an autosomal dominant model with 90% penetrance and an autosomal recessive model with full penetrance. A linear age-of-onset correction with maximum penetrance at age 20 years was incorporated into the analyses. The maximum lod score obtained was 3.11 at (-)m = 0.001, (-)f = 0.20, assuming autosomal dominant inheritance and using the second definition of the disease phenotype. There was strong support for linkage using the other phenotype definitions and the autosomal dominant model, although the lod scores did not exceed 3.0. There was also support for linkage of a JME locus to this region under the autosomal recessive model, although the results varied depending upon the definition of the disease phenotype. There was no significant evidence for linkage heterogeneity.

Chromosome Mapping↗
PubMed1991

Localization of idiopathic generalized epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients.

Juvenile myoclonic epilepsy (JME) is a distinct subform of idiopathic generalized epilepsy of adolescence. Linkage studies with Bf and serologic HLA markers in families of JME patients have shown a tight linkage on chromosome 6. We present a linkage analysis with HLA-DQ restriction fragment length polymorphisms on more extended families, paying particular attention to the epilepsy type of the affected family members. We studied 21 families of JME patients with a total of 143 family members and obtained a highest logarithm of the odds (lod) score of 3.9 (theta m = 0.01, theta f = 0.01) assuming a dominant mode of inheritance and 70% penetrance when family members with JME, absence epilepsy, or epilepsy with generalized tonic-clonic seizures (GTCS) were considered as affected. When we also classified clinically normal family members with generalized spike-wave discharges in the EEG as "affected," the maximum lod score was 4.1 (theta m = 0.01, theta f = 0.3) under a dominant mode of inheritance and 90% penetrance. These findings support the conclusion that a gene locus for a group of idiopathic generalized epilepsies (JME, epilepsy with absences, and epilepsy with GTCS) maps to chromosome 6p.

Chromosomes, Human, Pair 6↗
PubMedDate not supplied

Possible association of juvenile myoclonic epilepsy with HLA-DRw6.

Juvenile myoclonic epilepsy (JME) is a clearly defined subform of idiopathic generalized epilepsy with a high aggregation of epilepsy in family members. With the HLA-system used as a genetic marker, a linkage between JME and the HLA region was demonstrated. Linkage with the HLA region suggests that JME may be associated with an HLA-antigen. An association could indicate that the gene lies in the HLA region and is in linkage disequilibrium with one of the HLA-antigens. Eighty-eight unrelated patients with JME were typed for the HLA-A and HLA-B locus, 77 were typed for the HLA-C locus, and 76 were typed for the DR locus. The antigen frequency was compared with those of healthy blood donors. The highest difference was noted in the frequency of DRw6 (39.5% in patients vs. 22.1% in controls). This weak association is open to question because DRw6 is known to split into DRw13 and DRw14.

Epilepsies, Myoclonic↗
PubMedDate not supplied

Phenocopies versus genetic heterogeneity: can we use phenocopy frequencies in linkage analysis to compensate for heterogeneity?

In this study we explore whether a phenocopy frequency (defined as a "penetrance' for nondisease genotypes) can approximate or model genetic heterogeneity in a single-locus analysis. We simulated two types of heterogeneity situations: "sporadic models', where there are two forms of a disease, one genetic and linked to a marker and the other purely random, and "genetic heterogeneity models', where the disease is caused by either of two different loci, one linked to the marker and the other unlinked. We analyzed simulated data sets for linkage, assuming a single-locus analysis with varying phenocopy frequency, in analogy with earlier work on epistatic two-locus models. We found that in the presence of purely random sporadics, there was a difference between assuming any nonzero phenocopy frequency and a zero frequency, but that the actual value of the assumed phenocopy frequency had little effect on the maximum lod score. In contrast, when both forms of disease are genetic, and are generated under similar genetic parameters, assuming a positive phenocopy frequency will not, in general, compensate for the presence of the unlinked form. However, when the modes of inheritance of the two forms differ, the assumption of a nonzero phenocopy frequency does have an effect, either to increase or decrease the maximum lod score, depending on the modes of inheritance of the two disease forms. We conclude with practical recommendations for investigators, based on these results.

Gene Frequency↗