Rapid molecular discrimination between infection with wild-type varicella-zoster virus and varicella vaccine virus.

Varicella-zoster virus (VZV) infection is immunocompromised patients may cause life-threatening complications. Prevention measures include administration of VZV immuloglobulin, acyclovir and live attenuated varicella vaccine. After vaccination, a mild varicella-like exanthem appears in up to 5% of vaccinees. Morphologically this exanthem cannot be differentiated from wild-type (wt) varicella. The risk of virus transmission after varicella vaccination, in contrast to wt varicella, is low, even in immunocompromised patients. We report on a 2-year-old girl with relapse of cereral anaplastic ependymoma, who received one dose of varicella vaccine. Two weeks later, a maculopapular rash developed while she was an inpatient on the oncology ward. Using VZV-specific PCR and restriction fragment length polymorphism (RFLP) analysis, we were able to diagnose wt varicella infection. Thus, appropriate prevention measures (VZV immunoglobulin and acyclovir) were justified for close contacts to prevent virus transmission. No secondary cases occurred.

Tetrahydrobiopterin responsiveness in phenylketonuria. Two new cases and a review of molecular genetic findings.

We report two new patients with tetrahydrobiopterin (BH4)-responsive phenylketonuria and compare their phenylalanine hydroxylase (PAH) genotypes (A395P/ IVS12+g>a and R261Q/165T, respectively) to those of previous cases from the literature. These case observations confirm earlier reports stating that BH4-responsive patients are frequently carriers of a missense mutation within the DNA region coding for the catalytic domain of the enzyme. Interestingly, many of the PAH gene mutations detected in BH4-responsive patients have been associated with an inconsistent phenotype in the past. Our case reports confirm that it is necessary to thoroughly examine individuals with increased phenylalanine levels, not only to detect BH4 deficiency, but also to identify patients with PAH deficiency who may benefit from BH4 treatment. In both of our patients, however, an effect of BH4 (7.5 mg/kg) on plasma phenylalanine levels was not seen in the newborn period. We therefore conclude that a normal neonatal BH4 test does not necessarily exclude BH4 responsiveness in all such patients.

Centrotemporal spikes in families with rolandic epilepsy: linkage to chromosome 15q14.

OBJECTIVE: To localize a gene predisposing to benign epilepsy of childhood with centrotemporal spikes (BECTS). BACKGROUND: BECTS, or rolandic epilepsy, is the most prevalent idiopathic epilepsy syndrome in childhood. Functional relevant defects in the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (AChR) have been demonstrated in autosomal dominant nocturnal frontal lobe epilepsy, which, like BECTS, is an idiopathic partial epilepsy. METHODS: A DNA linkage study was conducted screening all chromosomal regions known to harbor neuronal nicotinic AChR subunit genes. Twenty-two nuclear families with BECTS were analyzed. RESULTS: In an "affected-only" study, best p values and lod scores were reached between D15S165 and D15S1010 on chromosome 15q14. In multipoint nonparametric linkage analysis a nominal p value of 0.000494 was calculated by GENEHUNTER. Best parametric results were obtained under an autosomal recessive model with heterogeneity (multipoint lod score 3.56 with 70% of families linked to the locus). These markers are localized in direct vicinity to the alpha 7 subunit gene of the AChR. CONCLUSIONS: We found evidence for linkage of BECTS to a region on chromosome 15q14. Either the alpha 7 AChR subunit gene or a closely linked gene are implicated in pedigrees with BECTS. The disorder is genetically heterogeneous. Surprisingly, the same chromosomal area has been reported to be linked to the phenotype in families with an auditory neurophysiologic deficit as well as in families with juvenile myoclonic epilepsy, another idiopathic but generalized epilepsy syndrome.

Benign childhood epilepsy with centrotemporal spikes and electroencephalography trait are not linked to EBN1 and EBN2 of benign neonatal familial convulsions.

PURPOSE: The electroencephalographic hallmark of benign childhood epilepsy with centrotemporal spikes (BECTS, or rolandic epilepsy) are characteristically shaped centrotemporal spikes and sharp waves (CTS). This EEG trait, but not BECTS itself, has been reported to follow an autosomal dominant mode of inheritance with incomplete penetrance and age dependence. CTS therefore represents a neurobiologic marker for the increased risk of developing BECTS. Benign neonatal familial convulsions (BNFC) like BECTS is an idiopathic age-dependent epilepsy with a benign course. Observations of benign neonatal seizures and BECTS in the same individual are well documented. Neonatal seizures with benign course were found in increased numbers in a series of CTS carriers. Two genetic loci, EBN1 and EBN2, have been mapped in families with BNFC, making these two loci strong candidates for the CTS trait underlying BECTS. The aim of this study was to determine whether these two epilepsy syndromes are allelic disorders. METHODS: Linkage analysis was performed in 12 families with probands with BECTS and one or more relatives with CTS in the EEG with or without BECTS by using polymorphic DNA markers. RESULTS: Assuming an autosomal mode of inheritance with penetrances of 0.9 and 0.45, respectively, both loci were consistently excluded. CONCLUSIONS: The CTS trait and EBN1 and EBN2 segregate independently. BECTS and BNFC therefore appear to be genetically distinct entities. Benign neonatal seizures may be a underrecognized symptom of the CTS trait itself.