1/15. Human genetic disease caused by de novo mitochondrial-nuclear dna transfer.Transfer of nucleic acid from cytoplasmic organelles to the nuclear genome is a well-established mechanism of evolutionary change in eukaryotes. Such transfers have occurred throughout evolution, but so far, none has been shown unequivocally to occur de novo to cause a heritable human disease. We have characterized a patient with a de novo nucleic acid transfer from the mitochondrial to the nuclear genome, a transfer that is responsible for a sporadic case of pallister-hall syndrome, a condition usually inherited in an autosomal dominant fashion. This mutation, a 72-bp insertion into exon 14 of the GLI3 gene, creates a premature stop codon and predicts a truncated protein product. Both the mechanism and the cause of the mitochondrial-nuclear transfer are unknown. Although the conception of this patient was temporally and geographically associated with high-level radioactive contamination following the Chernobyl accident, this case cannot, on its own, be used to establish a causal relationship between radiation exposure and this rare type of mutation. Thus, for the time being, it must be considered as an intriguing coincidence. Nevertheless, these data serve to demonstrate that de novo mitochondrial-nuclear transfer of nucleic acid is a novel mechanism of human inherited disease.- - - - - - - - - - ranking = 1keywords = organ (Clic here for more details about this article) |
2/15. A case of familial popliteal pterygium syndrome: early surgical intervention for successful treatment.A 2-year-old boy presented at our hospital with severe familial popliteal pterygium syndrome with extensive skin webbing from thigh to heel and severely reduced range of motion of the knee and ankle joints. For accomplishment of knee extension, the patient underwent surgery with resection of the fibrous bands, freeing of the sciatic nerve, Z-lengthening of the achilles tendon and multiple Z-plasties. One year after surgery, the patient can put his heel on the ground and has almost complete range of motion in the knee and ankle joints.- - - - - - - - - - ranking = 0.47443678702018keywords = nerve (Clic here for more details about this article) |
3/15. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.Ca(V)1.2, the cardiac L-type calcium channel, is important for excitation and contraction of the heart. Its role in other tissues is unclear. Here we present Timothy syndrome, a novel disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. In every case, Timothy syndrome results from the identical, de novo Ca(V)1.2 missense mutation G406R. Ca(V)1.2 is expressed in all affected tissues. Functional expression reveals that G406R produces maintained inward Ca(2 ) currents by causing nearly complete loss of voltage-dependent channel inactivation. This likely induces intracellular Ca(2 ) overload in multiple cell types. In the heart, prolonged Ca(2 ) current delays cardiomyocyte repolarization and increases risk of arrhythmia, the ultimate cause of death in this disorder. These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2 ) signaling in autism.- - - - - - - - - - ranking = 1keywords = organ (Clic here for more details about this article) |
4/15. Inv dup (15): is the electroclinical phenotype helpful for this challenging clinical diagnosis?OBJECTIVE: To study the electroclinical phenotype in 5 patients with large supernumerary marker chromosome referred as inv dup (15), in an attempt to analyze the electroclinical spectrum in order to determine if the binomial epilepsy-EEG is stereotyped enough to corroborate this challenging diagnosis. methods: Five patients with large inv dup (15) were submitted to EEG and/or V-EEG, with a minimum duration of 2h. Two certified neurophysiologists analyzed all EEG tracings simultaneously, blinded to clinical and molecular data. epilepsy was characterized by detailed history and a standard questionnaire according to International League Against epilepsy guidelines and corroborated by V-EEG findings. RESULTS: epilepsy started during infancy in 4 patients, in 3 with spasms. Spasms were easily controlled in one but not in others. epilepsy evolved with generalized seizures in two patients and, generalized and focal in one. Currently, 3 patients present refractory epilepsy and two are seizure-free. In one patient, only one isolated episode suggestive of a secondary generalized tonic-clonic event occurred at the age of 12 years without recurrence. Regarding the EEG, patients had distinct features, except for two patients with very high amplitude fast activity, resembling recruiting rhythm. Despite good seizure outcome in 3 patients, EEGs remained remarkably abnormal with frequent epileptiform discharges over poorly organized background. CONCLUSIONS: Our data showed a heterogeneous electroclinical phenotype with generalized and partial epilepsy, presenting distinct degrees of severity and refractoriness. SIGNIFICANCE: Our findings suggest that it is not possible to delineate an electroclinical phenotype in this neurogenetic syndrome. Therefore, inv dup (15) remains as a diagnostic challenge and epilepsy and EEG features are valuable only when inserted in the proper clinical context.- - - - - - - - - - ranking = 1keywords = organ (Clic here for more details about this article) |
5/15. Benign hereditary cerebellar ataxia with extensive thermoanalgesia.A new zealand family with 3 members affected by late onset hereditary cerebellar ataxia is reported, distinguished by the development of near global thermoanalgesia. Because proprioception and autonomic function were preserved, and ataxia only slowly worsened, this proved to be a benign syndrome. The pattern of sensory loss indicated a 'length-dependent' neuropathy. Evaluation of sural nerve biopsy revealed a marked loss of axons, especially of those with diameters 1-7 microns and 0.2-1.5 microns. It therefore seemed likely that impairment of pain and temperature in the syndrome resulted from a loss of primary sensory afferents. It is concluded that this family represents a previously unrecognized variant and that the spectrum of hereditary ataxias needs to be widened to include an associated severe but selective loss of pain and temperature sensation.- - - - - - - - - - ranking = 0.47443678702018keywords = nerve (Clic here for more details about this article) |
6/15. Conceiving a fetus for bone marrow donation: an ethical problem in prenatal diagnosis.We present a family who sought prenatal diagnosis in order to bear a healthy child to serve as an HLA-identical bone marrow donor for their son affected with wiskott-aldrich syndrome. They intended to abort HLA-incompatible fetuses who would have been unsuitable bone marrow donors. This case led us to conclude that prenatal diagnosis should not be used to benefit a third party or facilitate the conception or abortion of a fetus for the purpose of generating an organ for transplantation. The limits of parental autonomy and physician responsibility are discussed.- - - - - - - - - - ranking = 1keywords = organ (Clic here for more details about this article) |
7/15. Juvenile diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, atonia of the urinary tract and bladder, and other abnormalities (wolfram syndrome). A review of 88 cases from the literature with personal observations on 3 new patients.A review of 88 cases from the literature with personal observations on 3 new patients is given of the syndrome featured by juvenile diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, atonia of the urinary tract and bladder and other abnormalities. The postmortem in one of our cases is mentioned. The pattern of inheritance is autosomal recessive. The interpretation of the data on diabetes insipidus from the literature and in our three patients is also discussed. It can only be stated that neurohypophyseal diabetes insipidus can be a component of the syndrome and that in many cases--particularly in the presence of lesions of the efferent urinary tract--the possibility of nephrogenous diabetes insipidus can not be excluded with certainty. It seems probable that the same mechanism can be held responsible for the lesions of the olfactory, optic, vestibular and cochlear nerves, the hypophyseal form of diabetes insipidus, retarded sexual maturation, abnormal pupillary reaction, myelopathy and the electro-encephalographic, electroneurological and electromyographic changes in the wolfram syndrome. The process underlying this affection of neural structures remains obscure.- - - - - - - - - - ranking = 0.47443678702018keywords = nerve (Clic here for more details about this article) |
8/15. Ocular findings in a new heritable syndrome of brain, eye, and urogenital abnormalities.We studied the clinical and histopathologic ocular findings in four related males with a newly recognized syndrome consisting of microphthalmos, microencephaly, mental retardation, agenesis of the corpus callosum, hypospadius, and cryptorchidism with X-linked recessive inheritance. The ocular abnormalities include microphthalmos, corneal pannus and hypoplasia, cataracts, uveal hypoplasia, retinal dysplasia, optic nerve hypoplasia, and congenital blepharoptosis. In case 4, a female twin who died in utero (at 15 weeks' gestation) showed none of the ocular abnormalities.- - - - - - - - - - ranking = 0.47443678702018keywords = nerve (Clic here for more details about this article) |
9/15. Peripheral and central conduction times in hereditary pressure-sensitive neuropathy.Seven members of a family with histologically proven hereditary pressure-sensitive neuropathy (HPSN) agreed to be examine clinically and electrophysiologically. A sural nerve biopsy specimen taken from the propositus who suffered from a partial brachial plexus palsy showed typical 'sausage-like' myelin sheath thickenings reflecting a failure of axon-adjusted myelination. Reduced motor and sensory conduction velocities involving several nerves were found in the four family members with clinical signs of HPSN. In addition, central conduction times in the auditory and somatosensory pathways were determined measuring the interwave latency I-V in brainstem auditory-evoked potentials and the interpeak latency N14-N20 in median nerve sensory-evoked potentials. Central conduction times in both afferent systems were within normal limits. The absolute delay of peak N14 and N20 in median and P40 in tibial nerve-evoked potentials was probably due to an impaired conduction in the peripheral branch of the bipolar ganglion cell. Whether the central axon branch in the dorsal columns was also involved could not be decided.- - - - - - - - - - ranking = 1.8977471480807keywords = nerve (Clic here for more details about this article) |
10/15. Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family.A hereditary ceruloplasmin deficiency associated with severe iron deposition in visceral organ and brain tissues found on histopathological examination at autopsy is discussed. Three siblings of consanguineous Japanese parents were studied. Their clinical symptoms were progressive dementia, extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus, all of which appeared when they were between 30 and 50 years old. All had serum ceruloplasmin deficiencies and increased serum ferritin concentrations. The dentate nucleus, thalamus, putamen, caudate nucleus, and liver of each one showed low signal intensities on T1- and T2-weighted magnetic resonance images. Examination of the central nervous system revealed severe destruction of the basal ganglia and dentate nucleus, with considerable iron deposition in neuronal and glial cells, whereas the cerebral cortex showed mild iron deposition in glial cells without neuronal involvement. An electron microscopic study with energy-dispersive x-ray analysis showed iron depositions in the hepatocytes, of both the neural and glial cells of the brain. We consider this a new disease entity because of the primary ceruloplasmin deficiency.- - - - - - - - - - ranking = 1keywords = organ (Clic here for more details about this article) |
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