Successful DNA-based prenatal exclusion of juvenile neuronal ceroid lipofuscinosis

A family with two siblings, 10 and 8 years old, both with clinical and ultrastructural evidence of juvenile neuronal ceroid lipofuscinosis is described. The family was found to be informative for the restriction fragment length polymorphisms (RFLPs) detected by the probes pCJ52–95Ml (locus D16S148) and pCJ52-94Tl (locus D16S159) flanking the juvenile neuronal ceroid lipofuscinosis locus, CLN3. The parents were both heterozygous using these probes, while their two children with juvenile neuronal ceroid lipofuscinosis were both homozygous. Chorionic villi analysis showed that the fetus was heterozygous and had inherited the one allele of the mother which was not found in the two siblings. This suggested that the fetus had derived one healthy allele from the mother, the risk for a double crossing-over being less than 1 per cent. Electron microscopy showed no fingerprint inclusions in chorionic villi. The child was investigated at 6 months of age and found to be healthy, as new fingerprint inclusions were found at electron microscopy and no vacuolated lymphocytes were found in the blood smear. Due to the risk of heterogeneity, both DNA-based analysis and electron microscopy on chorionic villi are recommended for prenatal examination for juvenile neuronal ceroid lipofuscinosis.     

Fetal tissue involvement in the late infantile type of neuronal ceroid lipofuscinosis

Prenatal diagnosis in a pregnancy at risk for late infantile neuronal ceroid lipofuscinosis (Batten's disease) was undertaken at 17 weeks' gestation by ultrastructural examination of amniotic fluid cells. The presence of curvilinear profiles indicated an affected fetus and the diagnosis was confirmed, after the pregnancy was terminated, by the finding of many typical curvilinear profiles in multiple tissues which included skin, amnion, umbilical vessels, blood, liver, and brain. Comparison between the involved cells in the amniotic fluid and fetal tissues suggests that these cells are probably derived from the periderm, and possibly also from the amnion. The prominent presence of cytosomes in the periderm and intermediate cells of the fetal epidermis and occasionally also in the endothelial cells of the dermis suggests that fetal skin may be a useful alternative site for assessing fetal involvement. Control specimens of the amniotic fluid, fetal skin, amnion, and liver showed no similar cytosomes. However, some control amniotic fluid samples did contain cells with large collections of irregular trilaminar membranes, and these could be open to misinterpretation. It is important that only typical curvilinear profiles are considered as an indication of an affected pregnancy.     

50 Hz alternating extremely low frequency magnetic fields affect excitability,firing and action potential shape through interaction with ionic channels in snail neurones

In spite of growing concern about the influence of magnetic fields on biological systems, the interaction between extremely low frequency magnetic field (ELF magnetic fields) and biological structures at the cellular level remains obscure. The aim of this study was to investigate if 50 Hz magnetic fields could have an effect on the neuronal excitability and firing responses. Under Current-Clamp condition, exposure to 50 Hz ELF magnetic fields at 2 mT or 0.8 mT intensities resulted in an increase in the peak amplitude of action potential and after hyperpolaization potential in a time dependent manner. Both magnetic field intensities decreased also the firing frequency and the duration of action potential. Taken together, these data suggest that 50 Hz ELF magnetic fields at 2 mT or 0.8 mT intensities may change the electrophysiological behavior of neuronal cells and underlying ion channel currents.     

Inhibition of rhythmic neural spiking by noise: the occurrence of a minimum in activity with increasing noise

The effects of noise on neuronal dynamical systems are of much current interest. Here, we investigate noise-induced changes in the rhythmic firing activity of single Hodgkin–Huxley neurons. With additive input current, there is, in the absence of noise, a critical mean value μ = μ _c above which sustained periodic firing occurs. With initial conditions as resting values, for a range of values of the mean μ near the critical value, we have found that the firing rate is greatly reduced by noise, even of quite small amplitudes. Furthermore, the firing rate may undergo a pronounced minimum as the noise increases. This behavior has the opposite character to stochastic resonance and coherence resonance. We found that these phenomena occurred even when the initial conditions were chosen randomly or when the noise was switched on at a random time, indicating the robustness of the results. We also examined the effects of conductance-based noise on Hodgkin–Huxley neurons and obtained similar results, leading to the conclusion that the phenomena occur across a wide range of neuronal dynamical systems. Further, these phenomena will occur in diverse applications where a stable limit cycle coexists with a stable focus.     

Social experience influences the development of a central auditory area

Vocal communication develops under social influences that can enhance attention, an important factor in memory formation and perceptual tuning. In songbirds, social conditions can delay sensitive periods of development, overcome learning inhibitions and enable exceptional learning or induce selective learning. However, we do not know how social conditions influence auditory processing in the brain. In the present study, we raised young naive starlings under different social conditions but with the same auditory experience of adult songs, and we compared the effects of these different conditions on the development of the auditory cortex analogue. Several features appeared to be influenced by the social experience, among which the proportion of auditory neuronal sites and the neuronal selectivity. Both physical and social isolation from adult models altered the development of the auditory area in parallel to alterations in vocal development. To our knowledge, this is the first evidence that social deprivation has as much influence on neuronal responsiveness as sensory deprivation.     

Prenatal diagnosis of the infantile type of neuronal ceroid lipofuscinosis by electron microscopic investigation of human chorionic villi

Chorionic villus biopsy specimens were studied electron microscopically in six pregnancies at risk of the infantile type of neuronal ceroid lipofuscinosis (INCL). The biopsy was performed in all cases in the first trimester of pregnancy (8–10 gestation weeks) by the transcervical route. In one case, the biopsy was repeated at 17 weeks by the transabdominal procedure. In two pregnancies, the endothelial cells and, to a lesser extent, the mesenchymal cells of the chorionic villi contained unit membrane-bound inclusions typical of INCL. In both cases, the pregnancy was terminated and in one of them identical inclusions were found in the brains and kidneys of the fetus at 20 weeks of gestational age. The children from the remaining four pregnancies are healthy and have shown no signs of the disease.     

Probable exclusion of juvenile neuronal ceroid lipofuscinosis in a fetus at risk: An interim report

In a family with two children affected by juvenile neuronal ceroid lipofuscinosis (JNCL) an attempt was made at the prenatal diagnosis of the disorder. The following tissues from the fetus at risk were investigated by electron microscopy and were found to be free of fingerprint profiles and curvilinear bodies, typical for JNCL: uncultivated amniotic fluid cells, lymphocytes isolated from fetal blood, and fetal skin biopsy specimens. The child was born at the 34th week of gestation and was clinically normal at the age of 15 months. Postnatally, lymphocytes (isolated at the age of 6 and 15 months) and skin tissue (taken at the age of 15 months) were found to be morphologically normal. It is highly unlikely that the child is affected but definite proof of the absence of JNCL remains difficult at this age.     

Prenatal diagnosis and investigation of a fetus with chondrodysplasia punctata,ichthyosis, and Kallmann syndrome due to an Xp deletion

We report the prenatal diagnosis of a male fetus with X-linked recessive chondrodysplasia punctata (CDPX), steroid sulphatase (STS) deficiency, X-linked Kallmann syndrome (KAL), and a chromosome deletion at Xp22.31. Biochemical analysis of bone from this case indicates that CDPX is not a defect of vitamin K metabolism. Immunocytochemical study of the brain suggests that KAL is a defect in neuronal migration.     

Antenatal gene tests in low-risk pregnancies: molecular screening for aspartylglucosaminuria (AGU) and infantile neuronal ceroid lipofuscinosis (INCL) in Finland

Approximately one in five subjects in Finland carries some gene defect associated with 30 diseases belonging to the Finnish disease heritage, and about one in 500 children born is affected. Almost all carriers, women and men, are unaware of their condition. Recent advances in molecular medicine have offered the possibility of population-based carrier screening for recessive disorders. We studied acceptance and attitudes to antenatal screening for aspartylglucosaminuria (AGU) and infantile neuronal ceroid lipofuscinosis (INCL). From January 1995 until December 1996 carrier tests were offered at Kuopio City Health Center, free of charge to all pregnant women attending maternity care units. Women found to be carriers of AGU (n=47) or INCL (n=14) underwent detailed genetic counseling, and their male partners were also offered the test. If both partners appeared to be carriers we offered prenatal testing (n=1). No affected fetuses were detected. Attitudes towards the gene test were elicited by means of a questionnaire. Altogether 87% of pregnant women elected to undertake the gene tests. Antenatal screening for gene defects was feasible and well accepted, and it provided an effective way to find carriers of genetic diseases and to incorporate prenatal testing into this process. Copyright © 2001 John Wiley & Sons, Ltd.