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Biomedical subjects

D Janz

Publications and source records attributed to D Janz.

At least 19 recordsLinked to original sources
PubMed1992

Confirmation of the localization of the human GABAA receptor alpha 1-subunit gene (GABRA1) to distal 5q by linkage analysis.

The GABAA receptor is the major inhibitory neurotransmitter receptor in the mammalian brain. To date, 14 genes that encode subunits of this receptor have been identified; these appear to be scattered throughout the human genome and are under investigation as candidate loci for a number of neurological and psychiatric disorders. We report here a highly polymorphic (dC-dA)n repeat within the human alpha 1-subunit gene (GABRA1). Typing of this marker in the Centre d'Etude du Polymorphisme Humain (CEPH) panel of families confirms the previous assignment of the GABRA1 locus to the distal portion of chromosome 5q by demonstrating linkage to the markers CRI-L45 (D5S61) (Zmax = 11.00, theta max = 0.15), CRI-V1022 (D5S54) (Zmax = 7.25, theta max = 0.20), and CRI-P148 (D5S72) (Zmax = 5.71, theta max = 0.24).

Base Sequence↗
PubMed1992

Consensus guidelines: preconception counseling, management, and care of the pregnant woman with epilepsy.

All women with epilepsy who are of childbearing age should be advised (preferably before conception) that the incidence of malformations in infants of mothers with epilepsy who are treated with antiepileptic drugs (AEDs) is two or three times that of infants of mothers without epilepsy. In addition, children of mothers with epilepsy, treated or untreated with AEDs, tend to have slightly more minor anomalies than do children of fathers with epilepsy or control subjects. We do not know which of the four major AEDs (phenytoin, carbamazepine, valproate, and phenobarbital) is the most teratogenic. If AED treatment cannot be avoided, the first-choice drug for the seizure type and epilepsy syndrome should be used as monotherapy at the lowest effective dose. Diet prior to conception and during organogenesis should contain adequate amounts of folate. Prenatal diagnosis of possible birth defects should be offered, and patients should be followed closely during pregnancy, labor, and puerperium. Despite the small but significant risks, more than 90% of women with epilepsy who receive AEDs during pregnancy will deliver normal children free of birth defects.

Abnormalities, Drug-Induced↗
PubMed1992

Do idiopathic generalized epilepsies share a common susceptibility gene?

Molecular genetic research in epilepsy is most promising in the homogeneous, genetically determined forms of the disease. The phenotype-genotype strategy used makes some epileptic syndromes more suitable for such study than others. Unequivocal clinical presentation, mendelian transmission with similar clinical expression in close relatives, and sufficiently large numbers of affected families are requisites. This makes idiopathic generalized epilepsies (IGEs), particularly absence and juvenile myoclonic epilepsies (JMEs), suitable subtypes for genetic analysis. Results of family studies to date show that five IGE syndromes have a common genetic origin. Linkage studies have localized a gene defect on chromosome 6p that predisposes to a group of IGEs: JME, absence epilepsy, and generalized tonic-clonic seizures in epilepsy families with JME probands. Environmental and additional genetic factors are other areas requiring further study to elucidate the discriminant factors associated with different varieties of IGE.

Chromosomes, Human, Pair 6↗
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↗
PubMed1989

The temporal sequence of aura-sensations in patients with complex focal seizures with particular attention to ictal aphasia.

The sequences of aura sensations in 143 patients with complex partial seizures, were analysed with special emphasis on aphasic symptoms. Anxiety, epigastric sensation and visual hallucination were experienced early in the course of the aura, while illusion of familiarity and aphasia occurred late in the course of the aura. Three groups of interconnections of aura sensations were found which corresponded possibly to the types of seizure constellations proposed by Weiser. Close interconnections between impairment of verbal comprehension during seizures and paroxysmal thought disorder, as well as between paroxysmal paraphasia and illusion of familiarity were noted. Paroxysmal aphasia in patients with complex partial seizures was characterised as a positive symptom in contrast to stable aphasia.

Aphasia↗
PubMed1988

Neurological morbidity of severe epilepsy.

The "severity" of a disease is a relative expression and its definition will vary depending on the perspective of the observer. The patient's subjective perception of the disease, the way it is regarded socially by the community, and the doctor's objective assessment rarely coincide. In fact, they are frequently diametrically opposed. As far as the patient's personal perception of epilepsy is concerned, there has apparently been no satisfactory attempt thus far at a systematic grading of the subjective handicap, despite the growth of interest in psychological matters and the self-help movement. Similarly, social ability or disability cannot be adequately assessed on the basis of medical criteria such as frequency and type of seizures. We present a grading system which will serve as an example of an appropriate method of assessing social abilities, and which will permit the patient's occupational potential to be estimated in relation to the risk of accidents resulting from seizures. From the medical point of view, the impairment of a patient's abilities due to epilepsy is a function of the patient's responsiveness to treatment. We present a critical review of the factors which have an effect on the therapeutic prognosis: the causes of epilepsy, underlying structural lesions, the incidence of convulsive status epilepticus, various types of attacks, and the different epileptic syndromes. Taking two examples--epilepsy presenting in the form of absence and epilepsy with complex focal seizures--we show that ultimately the "severity of epilepsy" can only be defined from the medical standpoint on the basis of several factors whose value is of a predictive nature.

Brain↗
PubMed1985

Epilepsy with impulsive petit mal (juvenile myoclonic epilepsy).

Juvenile myoclonic epilepsy (JME) is a special syndrome within the primary generalized epilepsies which is characterized clinically by irregular jerks of shoulders and arms (so-called impulsive petit mal) after awakening and electroencephalographically by bilateral-synchronous 4-6/s spike-wave complexes, often in the form of multispike-waves. The age of onset for this syndrome which occurs in 4-6% of all epilepsies is predominantly between 12 and 18 years. It mostly starts with isolated jerks which as a rule are soon followed by generalized tonic-clonic seizures (TCS). Jerks and TCS are provoked by sleep deprivation and predominantly occur after awakening (awakening epilepsy). Sleep deprivation and photostimulation are also very efficient in provoking specific EEG patterns. Exogenous factors have no etiological significance. Genetic studies suggest a polygenetic mode of inheritance and a lower threshold of manifestation in women. JME can be controlled very well by valproate and/or primidone. A complete cure, nevertheless, does not seem to be possible. Within the group of primary generalized epilepsies beginning in adolescence JME is closely related nosologically to the syndrome of juvenile absences and the syndrome of pure grand mal on awakening.

Adolescent↗
PubMed1985

Febrile seizures in patients with complex partial seizures.

Febrile seizures occurred in 14 of 155 (9%) out-patients with complex partial seizures. Twelve patients had prolonged or recurrent febrile seizures, convulsive status epilepticus or a transient postictal neurological deficit. Febrile seizures were associated with perinatal abnormalities, an earlier onset of epilepsy and with a poor seizure control. Recurrent febrile seizures or those with complicating features are associated with an unfavourable therapeutic outcome in adult patients with complex partial seizures.

Adult↗