Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This joint work has studied the cardiomyopathies occurring in hereditary neuro-muscular disorders (270 cases). The Duchenne type of disorder (74 cases) was responsible for asystole (4 cases), for cardiomegaly, and especially for abnormalities of the ECG (59 cases)--Q waves and large R waves in V1 and V6. The cardiomyopathy was of the hypokinetic type, with histological evidence of degeneration of the myocardial fibres. Dystrophia myotonica of Steinart (23 cases) caused conductive disorders (17 cases) which were either atrioventricular or intra-ventricular or both. Studies of the His pathway confirmed that these abnormalities were more diffuse in 5 cases. The main histological feature was interstitial fibrosis. There was a high risk of sudden death; ECG follow-up should be close. Friedreich's disease (20 cases) in its complete form led to later development of obstructive cardiomyopathy, with a systolic ejection murmur, cardiomegaly, and abnormalities of the ECG--left ventricular hypertrophy in the vertical axis, right ventricular and septal hypertrophy, repolarisation disorders similar to those found in coronary artery disease. Histology showed hypertrophy with degeneration of the myocardial fibres and interstitial fibrosis. This complete form was rare (7 cases out of 20); on the other hand, ECG abnormalites were very common (16 cases out of 20). The authors have tried to study the relationships between primary cardiomyopathies (50 cases) and peripheral neuromuscular disorders. 17 of the 39 peripheral muscle biopsies were abnormal, but a well-defined muscular dystrophy could not be found in them.
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PMID:[The myocardiopathies of hereditary neuro-muscular diseases]. 9 58

Bipolar electrode catheter recordings of His bundle electrograms with three simultaneously recorded surface electrocardiographic leads were obtained from 30 pediatric and adolescent patients (aged 3 to 18 years). In 14 patients, cardiac murmurs were proved to be innocent by cardiac catheterization. The control conduction intervals were compared to those of 13 patients with congenital heart disease, and three with acquired heart disease (myocardiopathy, rheumatic valvular disease, and Friedreich's ataxia). P-R, intra-atrial (P-A), A-V nodal (A-H), and intraventricular (H-V) conduction intervals were measured to the nearest 5 msec. Conduction delays were analyzed in each of the three components of the P-R interval. These delays occurred both in single components of the system as well as in combined conduction delays and were not always demonstrable by surface electrocardiograms. The Wenckebach phenomenon induced by atrial pacing was localized to the A-V node as well as the His-Purkinje system. This technique of intracardiac electrogram recordings is safe, does not significantly prolong cardiac atheterization time, and often yields unique and useful data concerning A-V conduction.
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PMID:A His bundle electrocardiographic analysis of cardiac conduction in the pediatric and adolescent patient. 111 61

Three children with hair-shaft abnormalities and neurological disorders are reported. The first case is a young girl with monilethrix and Friedreich's ataxia that presented IgG and IgA deficiency, without telangiectasis. The second patient is a young girl with monilethrix and HMSN I. The third patient is a boy with a peculiar face, hypotrichosis and pili torti; he was mentally retarded and had epileptic seizures. His diagnosis was compatible with Noonan's syndrome or with a cardio-facio-cutaneous syndrome, because of the existence of hyperkeratosis and the neurological features. It is our aim to emphasize the heterogeneity of neurotrichosis, whose limits are not well established and whose manifestations are shared by some of them.
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PMID:[Hair disorders and neurological impairments (neurotricosis): three new cases]. 749 1

Familial vitamin E deficiency (AVED) causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. AVED is thought to be caused by a defect in the transport of vitamin E in liver cells, which is the probable function of alpha-tocopherol transfer protein (alphaTTP). We have cloned the cDNA and several genomic phage clones covering the entire human alphaTTP gene and determined the junctions between the five exons and four introns that composed the gene for human alphaTTP. Three mutations in three unrelated North American families with AVED were identified. Two mutations, 485delT and 513insTT, cause a frame shift and a premature stop codon and the third mutation 574G-->A would substitute Arg192 to His in alphaTTP. The 2 patients with a severe form of AVED were homozygous with 485delT and 513insTT, respectively, while the patient with a mild form of the disease was compound heterozygous with 513insTT and 574G-->A. These findings have identified the underlying genetic defect in AVED and have confirmed the role of alphaTTP in AVED.
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PMID:Human alpha-tocopherol transfer protein: gene structure and mutations in familial vitamin E deficiency. 860 47

Friedreich ataxia is usually caused by an expansion of a GAA trinucleotide repeat in intron 1 of the FRDA gene. Occasionally, a fully expanded allele has been found to arise from a premutation of 100 or less triplet repeats. We have examined the sperm DNA of a premutation carrier. This man's leucocyte DNA showed one normal allele and one allele of approximately 100 repeats. His sperm showed an expanded allele in a tight range centering on a size of approximately 320 trinucleotide repeats. His affected son has repeat sizes of 1040 and 540. These data suggest that expansion occurs in two stages, the first during meiosis followed by a second mitotic expansion. We also show that in all informative carrier father to affected child transmissions, with the notable exception of the premutation carrier, the expansion size decreases.
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PMID:Sperm DNA analysis in a Friedreich ataxia premutation carrier suggests both meiotic and mitotic expansion in the FRDA gene. 973 27

CyaY is a 106-residue protein from Escherichia coli. It shows amino-acid sequence similarity to human frataxin and a frataxin homologue in Saccharomyces cerevisiae, Yfh1p. The former is associated with the disease Friedreich ataxia and the latter plays a key role in iron homeostasis in mitochondria. CyaY has been overexpressed in soluble form in E. coli. The recombinant protein with a His(6) tag at its C-terminus has been crystallized at 296 K using polyethylene glycol (PEG) 4000 as a precipitant. Native diffraction data have been collected to 1.8 A using Cu Kalpha X-rays. The crystals belong to the trigonal space group P3(1)21 (or P3(2)21), with unit-cell parameters a = b = 44.66, c = 99.87 A, alpha = beta = 90.0, gamma = 120.0 degrees. The asymmetric unit contains one molecule of recombinant CyaY, with a corresponding V(m) of 2.13 A(3) Da(-1) and solvent content of 42.3%.
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PMID:Crystallization and preliminary X-ray crystallographic analysis of Escherichia coli CyaY, a structural homologue of human frataxin. 1093 Aug 45

Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.
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PMID:Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. 1158 99

The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.
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PMID:The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. 1158

We report a 58-year-old man with slowly progressive muscle atrophy and weakness in the four extremities, accompanying cerebellar ataxia and sensory impairment of all modalities. He was a product of consanguineous marriage. His neurological manifestations began in childhood. He was admitted to our hospital because of marked abdominal distension and pretibial edema with hypoalbuminemia and hyperlipidemia. Neuroimaging studies showed marked atrophy of the cerebellum and spinal cord. Nerve conduction studies presented with slowing and sural nerve biopsy revealed demyelination with onion-bulbs. Abdominal distension was interpreted to be caused by chronic idiopathic intestinal pseudo-obstruction (CIIP), leading to protein-losing gastroenteropathy and hypalbuminemia caused by the CIIP. He died of DIC by myelodysplasic syndrome and DIC, two years later. Postmortem study demonstrated with severe loss of anterior horn cells and gliosis in the spinal cord. The Clarke's column was also affected. There was symmetrical degeneration in the dorsal column and corticospinal tracts. The cerebellum showed atrophy of molecular layer, prominent loss of Purkinje's cells and sparse granular cell layer, but no obvious change in the dentate nucleus. Neuronal loss in the dorsal root ganglia was remarkable. There were no alternations in the cerebral cortex, striatum, thalamus, subthalamic nucleus, and pontine nucleus, except for mild changes in substantia nigra and inferior olivary nucleus. This case was clinically suspected either of variant of Friedreich's ataxia or an early onset ataxia associated with hypoalbuminemia (EOAHA), although marked autonomic dysfunction was atypical. But the postmortem study, demonstrated with marked neuronal loss in anterior horn cells and cerebellan cortex and rather suggested an independent category of this case.
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PMID:[An autopsy case of atypical Friedreich's ataxia with chronic idiopathic intestinal pseudo-obstruction]. 1180 52

Fifteen Moroccan families with a phenotype resembling Friedreich Ataxia (FA) were studied. Seven families (13 patients) had the 744 del A mutation in the alpha-tocopherol transfer protein (alpha-TTP) gene, characteristic of ataxia with vitamin E deficiency (AVED). The other eight families (16 patients) had GAA expansions in the first intron of the frataxin gene. The clinical differences between the two groups differed. AVED caused by the 744 del A could be distinguished by head titubation, lower frequency of the neuropathy and slower disease progression, decreased visual activity and retinitis pigmentosa, which has also been associated with a His(101) Gln missense mutation in the alpha-TTP gene. The neurological disorder associated with vitamin E deficiency can be improved by the alpha-tocopherol treatment.
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PMID:Clinical comparison between AVED patients with 744 del A mutation and Friedreich ataxia with GAA expansion in 15 Moroccan families. 1203 60


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