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Isolation of a regulatory gene of anthocyanin biosynthesis in tuberous roots of purple-fleshed sweet potato.

Many transcriptional factors harboring the R2R3-MYB domain, basic helix-loop-helix domain, or WD40 repeats have been identified in various plant species as regulators of flavonoid biosynthesis in flowers, seeds, and fruits. However, the regulatory elements of flavonoid biosynthesis in underground organs have not yet been elucidated. We isolated the novel MYB genes IbMYB1 and IbMYB2s from purple-fleshed sweet potato (Ipomoea batatas L. Lam. cv Ayamurasaki). IbMYB1 was predominantly expressed in the purple flesh of tuberous roots but was not detected (or only scarcely) in other anthocyanin-containing tissues such as nontuberous roots, stems, leaves, or flowers. IbMYB1 was also expressed in the tuberous roots of other purple-fleshed cultivars but not in those of orange-, yellow-, or white-fleshed cultivars. Although the orange- or yellow-fleshed cultivars contained anthocyanins in the skins of their tuberous roots, we could not detect IbMYB1 transcripts in these tissues. These results suggest that IbMYB1 controls anthocyanin biosynthesis specifically in the flesh of tuberous roots. The results of transient and stable transformation experiments indicated that expression of IbMYB1 alone was sufficient for induction of all structural anthocyanin genes and anthocyanin accumulation in the flesh of tuberous roots, as well as in heterologous tissues or heterologous plant species.

Amino Acid Motifs↗

Lymphoblastoid lines and skin fibroblasts from patients with tuberous sclerosis are abnormally sensitive to ionizing radiation and to a radiomimetic chemical.

Lymphoblastoid lines, derived by transforming peripheral blood lymphocytes with Epstein-Barr virus, and skin fibroblast lines were established from two patients with tuberous sclerosis. The number of viable lymphoblastoid cells was determined by their ability to exclude the vital dye trypan blue after their irradiation with x-rays or 254 nm ultraviolet light. The growth of fibroblasts was determined by their ability to form colonies after treatment with the radiomimetic, DNA-damaging chemical N-methyl-N'-nitro-N-nitrosoguanidine. The tuberous sclerosis lymphoblastoid lines were hypersensitive to x-rays but had normal sensitivity to the ultraviolet radiation. The tuberous sclerosis fibroblast lines were hypersensitive to the N-methyl-N'-nitro-N-nitrosoguanidine. The hypersensitivity of tuberous sclerosis cells to x-rays and to N-methyl-N'-nitro-N-nitrosoguanidine is believed to reflect defective repair of DNA damaged by these agents and may provide the basis for in vitro, including prenatal, diagnostic tests for tuberous sclerosis.

Adolescent↗

CT and MR imaging of intracranial tuberous sclerosis.

CT and MR have permitted radiology to play a greater, but not definitive, role in detecting the pathologic components of tuberous sclerosis. SEN may be identified in only 80% of patients. Tubers are more ubiquitous and readily identified by MR in children and adults when the brain is myelinated. Since tubers are predominantly peripheral hypomyelinated lesions, the detection of small lesions may be delayed until an infant is over 16-18 months of age when the myelin will have extended to the junction between the cortical white and gray matter. SEGA typically evolve later during the first and second decades of life. Successful genetic counseling implies a need to detect tuberous sclerosis at a stage during infancy when imaging may fail to confirm the diagnosis, so tuberous sclerosis remains a clinical diagnosis.

Adolescent↗

An autopsy case of tuberous sclerosis associated with primary pericardial mesothelioma.

Tuberous sclerosis (Bourneville-Pringle phacomatosis) has been known to be associated with cardiac rhabdomyoma, but apparently never previously with primary pericardial mesothelioma. We present an autopsy case of this condition in a 59-year-old man, who had been diagnosed as having tuberous sclerosis in view of the presence of facial sebaceous adenoma, mental retardation, intracranial calcification, cerebral ventricular dilatation and renal tumor. During the clinical course, characterized by heart failure due to cardiac tamponade, cardiac sarcoma was diagnosed by imaging techniques. Autopsy revealed biphasic-type primary pericardial mesothelioma. As to the tuberous sclerosis, atypical giant cells in the tubers of the cerebral cortex and the lateral ventricular wall were found, which were considered to be derived from neurons rather than glial cells on the basis of staining with Bodian, Holzer, and antibodies against NSE, GFA and S-100 protein. In old tubers protruding into the lateral ventricles, fibrous glias were present with dense calcospherite deposits, coinciding with the CT findings. The renal tumors were angiomyolipomas, which were present bilaterally and showed partially infiltrative growth, but seemed to have a benign nature because of the lack of metastasis and atypism of the leiomyocytes.

Autopsy↗

Cardiac rhabdomyomas and their association with tuberous sclerosis.

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.

Echocardiography↗

On the incidence of fits and mental retardation in tuberous sclerosis.

OBJECTIVES: To establish the frequency of fits and mental retardation in an unbiased group of tuberous sclerosis patients. METHODS: Known tuberous sclerosis families with more than one affected person were ascertained for a genetic linkage study. A number of members were born after genetic counselling had been given after identification of the proband. These subjects were then carefully examined clinically and in many cases with cranial computerised tomography, renal ultrasound, and skeletal survey but not echocardiography. They provide an unbiased group of tuberous sclerosis patients and allow affected patients with normal intellect to be diagnosed. PATIENTS: Thirty-seven tuberous sclerosis families were ascertained and 26 patients born after the family proband were identified. RESULTS: Sixteen of these 26 patients suffered fits (62%) and 10 patients were mentally retarded (38%). CONCLUSIONS: A lower incidence of fits and mental retardation has been found in an unbiased sample of tuberous sclerosis patients. The lifetime risk for fits might be higher had we been able to follow the patients for longer. However, we believe these are more appropriate figures to use in genetic counselling for this disease.

Adolescent↗

Cystic renal involvement in tuberous sclerosis.

We describe two cases of unusual presentation of tuberous sclerosis with cystic renal involvement. A 19-month-old white male who was initially misdiagnosed as having polycystic kidney disease of "adult-type" developed petit mal seizures and small "ash-leaf" depigmented areas, raising a suspicion of tuberous sclerosis. Computerized tomography (CT) of the brain revealed periventricular calcifications, confirming the diagnosis of tuberous sclerosis. A 15 3/4-year-old black female with tuberous sclerosis showed acceleration of renal failure. Computerized tomography scan of the abdomen showed cystic lesions of the kidneys. In young children with cystic renal involvement but a negative family history of tuberous sclerosis or polycystic kidney disease, a CT scan of the brain should assist in the diagnosis. A CT scan or ultrasound examination of the abdomen will differentiate cystic renal lesions from angiomyolipoma of the kidneys.

Adolescent↗

Clinical role of positron emission tomography in children with tuberous sclerosis complex.

We evaluated the clinical role of positron emission tomography (PET) in 23 children with tuberous sclerosis complex. Mean age of the children when first scanned was 3.3 years. Mean age when seizures began was 8.7 months. All, except three, were at least mildly developmentally delayed. PET images were visually analyzed and compared to computed tomography (CT), magnetic resonance imaging (MRI), and the electroencephalogram (EEG). In two infants, interictal PET study was normal. One of the studies was performed with a low resolution early generation scanner at age 7 months; the other infant was 2 days old. Twenty-one of the 23 children had focal or multifocal cortical hypometabolism. Some hypometabolic cortical regions on PET did not show corresponding abnormalities on CT and MRI, and may be due to epileptogenic mechanisms or small tubers. PET provides additional localizing information to CT and MRI in patients with tuberous sclerosis complex. However, because of the normally low cerebral glucose metabolism in infancy, PET may give false negative findings if performed prior to about 1 year of age. The usefulness of glucose metabolism PET in most patients with tuberous sclerosis complex is limited. However, if the EEG, CT, and MRI abnormalities are unifocal or unilateral, and surgery is being contemplated, more detailed evaluation with PET may help to determine if contralateral tubers are present and evaluate the functional integrity of the brain as a whole.

Brain↗

Tuberous sclerosis complex and neonatal seizures.

Tuberous sclerosis complex is a multisystemic neurocutaneous disorder, manifesting variably during infancy and childhood that remains poorly described in neonates. When described in this population, tuberous sclerosis complex is most commonly associated with cardiac rhabdomyomas and brain tumors, but is rarely mentioned as an etiology for neonatal seizures. We report two children with tuberous sclerosis presenting for neonatal seizures. Neuroimaging findings of neonatal tuberous sclerosis complex are discussed. Given the absence of many of the traditional stigmata of tuberous sclerosis complex in the neonate, seizures should be considered an important presenting feature of this disorder in this particular age group.

Brain↗

Frost-susceptible protein in plasma membranes in tubers of Helianthus tuberosus L.

When plasma membranes were prepared from tubers of Helianthus tuberosus L. (Jerusalem artichoke) frozen at a sublethal temperature (-10 degrees C), the levels of some plasma membrane proteins, named frost-susceptible proteins (FSPs), decreased [Uemura, M., et al., Plant Physiol., 80, 187-195 (1986)]. The aim of this study was to characterize the response of FSP120, which is named FSP-3 in a previous report, to freezing treatment by immunoblotting. Levels of FSP120 in the plasma membranes of tubers decreased after sublethal freezing, whereas no degraded products were detected in the microsomes or the soluble fraction. The amount of FSP120 in the crude extract of frozen tubers remained at a comparable level to that of the unfrozen tubers. These results suggest that FSP120 might be released from plasma membranes during freezing treatment of the tubers of Jerusalem artichoke.

Cell Membrane↗

Cerebellar pathology in tuberous sclerosis.

Cerebellar involvement in tuberous sclerosis is rare and generally nonsymptomatic. The authors describe a cerebellar tuber in a 5-year-old boy with tuberous sclerosis. A CT scan at age 2 years showed the characteristic cortical, white matter, and subependymal lesions of tuberous sclerosis. At 5 years, when the patient was symptomatic with ataxia, the CT and MRI scans revealed additionally the presence of a right cerebellar enhancing lesion with edema. A total surgical resection was undertaken. The cerebellar lesion was very firm and demonstrated marked disorganization of neuronal architecture in the cerebellar folia, with bizzare ectopic neurons in the molecular and granule cell layers and white matter, along with calcification, gliosis, and Rosenthal fiber deposition. Balloon cells with glassy, pale, eosinophilic cytoplasm were also present. There was a marked loss of myelin in the white matter, with significant vacuolation and gliosis. Electron microscopy documented abundant lysosomal inclusions, prominent rough endoplasmic reticulum and Golgi complexes, microtubules, intermediate filaments, and synaptic contacts. While there is much speculation as to the precise nature of cerebellar pathology in tuberous sclerosis, this case demonstrates conclusively that the cerebellar lesions reflect anomolous neuronal development and migration akin to supratentorial lesions and can rarely be symptomatic.

Cerebellum↗

Pineal region giant cell astrocytoma associated with tuberous sclerosis: case report.

Tuberous sclerosis complex is a genetic disorder characterized by the development of hamartomas in multiple organs including the brain, skin, eye, kidney, and heart. Neurological features include seizures and mental retardation. Cortical tubers and subependymal nodules are the characteristic intracranial lesions of tuberous sclerosis. Subependymal giant cell astrocytomas, typically located adjacent to the foramen of Monro, can enlarge and cause symptomatic ventricular obstruction. The authors describe the case of a 3-year-old boy with a history of tuberous sclerosis and retinal lesions who presented with an enlarging enhancing pineal region mass. Via an infratentorial supracerebellar approach, the mass was removed using both the operative microscope and a rigid neuroendoscope. Pathological examination showed a giant cell astrocytoma. To the authors' knowledge, this is the first reported case of tuberous sclerosis associated with a giant cell astrocytoma of the pineal region. Diagnostic considerations are discussed.

Astrocytoma↗

Insulinoma in a patient with tuberous sclerosis: is there an association?

OBJECTIVE: To describe a patient with tuberous sclerosis who, on initial assessment, had neurologic symptoms, which were ultimately found to be caused by an insulinoma. METHODS: We present a case report with clinical, laboratory, and radiologic data. The literature is reviewed relative to tuberous sclerosis and islet cell tumors, and a possible association is discussed. RESULTS: A 43-year-old man with a history of tuberous sclerosis required medical attention because of mental confusion and slurred speech and was found to have hypoglycemia. Neuroradiologic imaging showed no new lesions to account for his symptoms. His physical examination was striking for a large abdominal mass, which showed increased uptake on octreotide scanning. After surgical resection, the mass measured 21 cm and was found to be an insulinoma. Blood glucose values were normal postoperatively and on follow-up, and the patient had no recurrence of the symptoms. CONCLUSION: From this report, we emphasize two findings. First, we draw clinicians' attention to the possibility of an association between islet cell tumors and tuberous sclerosis and suggest consideration of this diagnosis in patients with tuberous sclerosis who have new or worsening neurologic symptoms. Second, the insulinoma we describe is, to our knowledge, the largest to be reported thus far in the literature.

Adult↗

The localizing value of ictal SPECT in children with tuberous sclerosis complex and refractory partial epilepsy.

Although multiple cortical tubers are a hallmark of tuberous sclerosis complex (TSC), seizures often originate from a single tuber, making excisional surgery a therapeutic option for intractable patients. To assess the role of ictal single photon emission computed tomography (SPECT) in defining the epileptogenic tuber, we reviewed videoelectroencephalography (V/EEG) data, magnetic resonance imaging (MRI) and SPECT scans of 15 patients (aged 3 months to 15 years, mean 5.1) with medically resistant partial seizures and TSC. SPECT scans were performed using Tc-99m-hexamethylpropyleneamine oxime (HMPAO) injected within 30 seconds of electrographic seizure onset and were graded on a scale from 1 to 5 (1 weakly perfused, 5 strongly perfused). The scalp EEG revealed localized seizure origin in ten patients; five had concordant hyperperfused SPECT regions consisting of comma-shaped areas surrounding hypoperfused areas in the candidate tuber. Strongly hyperperfused regions (grade 3-5) were noted in two patients whose ictal EEG patterns were characterized by sustained, rhythmic fast activity or spiking. The other five patients had nonlocalizing or poorly sustained ictal EEG patterns; one patient in this group had focal hyperperfusion. Invasive EEG recordings in two patients revealed propagated EEG patterns that correlated with the ictal SPECT findings. These findings indicate a strong correlation between ictal SPECT and ictal scalp EEG, especially when there are sustained rhythmic fast ictal EEG patterns.

Adolescent↗

Mechanisms of unexpected death in tuberous sclerosis.

Tuberous sclerosis complex is a protean autosomal dominant disorder characterized by multifocal tissue lesions arising from defects in cellular migration, proliferation, and differentiation. It has an association with sudden death. In the current study, review of all cases of sudden death due to tuberous sclerosis was undertaken at the Forensic Science Centre in Adelaide, Australia from 1991 to 2001, in addition to an analysis of cases from the literature. There were two local cases where unexpected death had occurred in individuals with known tuberous sclerosis, involving a 31-year-old male (epilepsy), and a 24-year-old female (massive hemorrhage into a renal angiomyolipoma). Fatal mechanisms in cases of tuberous sclerosis may be associated with underlying cardiovascular, renal and cerebral abnormalities. Sudden death may be due to cardiac arrhythmia, epilepsy, and intra-tumoral hemorrhage with additional complications including cardiac outflow obstruction, obstructive hydrocephalus, aneurysm rupture, and spontaneous pneumothorax. An awareness of the highly variable tissue manifestations of tuberous sclerosis and the mechanisms that may be responsible for death is necessary to establish correctly the diagnosis in occult cases (possibly with molecular confirmation), and to chart accurately organ changes in individuals with established disease.

Adult↗

[A case of a pediatric patient with tuberous sclerosis (Bourneville-Pringle disease) and frequent epileptic seizure for intensive dental treatment under general anesthesia].

Tuberous sclerosis (Bourneville-Pringle disease) is a rare disease with a triad of mental retardation, epilepsy, and facial spot. Management of the patients with tuberous sclerosis under general anesthesia has been previously reported. However, there are few case reports about management under general anesthesia of a pediatric patient with tuberous sclerosis with frequent epileptic seizure. Here, we report a case of a pediatric patient with tuberous sclerosis and frequent epileptic seizure who underwent intensive dental treatment under general anesthesia with careful management of epilepsy. The patient was discharged on the day of surgery without any complications. In this case report, we discussed the appropriate assessment of the complications of tuberous sclerosis; such as, of central nervous, circulatory, respiratory, endocrine, and urinary systems including the management of general anesthesia.

Anesthesia, General↗

[Renal cell carcinoma associated with tuberous sclerosis: a case report].

Renal angiomyolipoma associated with tuberous sclerosis is well known. On the other hand, few cases of renal cell carcinoma in connection with tuberous sclerosis have been reported. We report a patient with tuberous sclerosis whose kidney was involved with renal cell carcinoma. A 18-year-old woman was first admitted in August 1987 for evaluation of left renal tumor. Diagnosis of tuberous sclerosis was made when she was 11 years old on the basis of mental retardation, papules on her face, seizures, white leaf-shaped macules and periventricular calcifications. Computerized tomographic scan demonstrated a large mass arising from the left kidney and small masses in the right kidney. Angiography confirmed bilateral hypervascular renal tumors. On these bases, a clinical diagnosis of bilateral renal angiomyolipomas was made and surgical treatment of the left kidney was recommended because of its large size. However, her parents did not permit treatment until March, 1988. Finally, left nephrectomy of 4,750 g was performed and histological examination revealed renal cell carcinoma with clusters of spindle cells. In the literature available to us, we found twelve reports of malignant renal tumors associated with tuberous sclerosis including five renal cell carcinomas in Japan.

Adolescent↗

[Precocious puberty revealing Bourneville tuberous sclerosis].

BACKGROUND: Benign tumors are seen in tuberous sclerosis. They are found in many organs, and the precocious puberty due to hypothalamic hamartoma and tuberous sclerosis has been reported. However, precocious puberty exceptionally reveals the tuberous sclerosis. CASE REPORT: A 2 month-old boy was admitted because of the fortuitous discovery of polycystic renal disease. Precocious puberty developed at 13 months with enlargement of the penis and testes, appearance of pubic hair, acne and deepening of the voice. Linear growth was recently accelerated and the bone maturation was advanced. Plasma testosterone was elevated (460 ng/100 ml) and LH-RH injection induced rapid rises in plasma LH (2.6 to 28 mUl/ml) and FSH (2 to 8 mUl/ml). Brain imaging techniques (CT scan and NMR) showed a hypothalamic hamartoma and periventricular calcified lesions. Examination with the Wood lamp identified two white leaf macules in the dorsal area. Administration of an analogue of LH-RH effectively reduced the manifestations of precocious puberty. CONCLUSION: Tuberous sclerosis is exceptionally revealed by precocious puberty. The association of polycystic disease and precocious puberty has never before been reported in tuberous sclerosis.

Hamartoma↗