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F Cardellach

Publications and source records attributed to F Cardellach.

At least 55 records · Page 3Linked to original sources
PubMed1996

A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome.

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (P<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

Adult↗
PubMed1996

Autosomal recessive Wolfram syndrome associated with an 8.5-kb mtDNA single deletion.

Wolfram syndrome (MIM 222300) is characterized by optic atrophy, diabetes mellitus, diabetes insipidus, neurosensory hearing loss, urinary tract abnormalities, and neurological dysfunction. The association of clinical manifestations in tissues and organs unrelated functionally or embryologically suggested the possibility of a mitochondrial implication in the disease, which has been demonstrated in two sporadic cases. Nonetheless, familial studies suggested an autosomal recessive mode of transmission, and recent data demonstrated linkage with markers on the short arm of human chromosome 4. The patient reported here, as well as her parents and unaffected sister, carried a heteroplasmic 8.5-kb deletion in mtDNA. The deletion accounted for 23% of mitochondrial genomes in lymphocytes from the patient and approximately 5% in the tissues studied from members of her family. The presence of the deletion in the patient in a proportion higher than in her unaffected parents suggests a putative defect in a nuclear gene that acts at the mitochondrial level.

Base Sequence↗
PubMed1995

[Progressive external ophthalmoplegia and the Kearns-Sayre syndrome: a clinical and molecular study of 6 cases].

The Kearns-Sayre syndrome (KSS) associates progressive external ophthalmoplegia initiating prior to the age of 20 years and pigmentary retinitis with a series of other heterogeneous clinical manifestations. The incomplete syndrome is usually denominated progressive external ophthalmoplegia (PEO)-plus which is a sporadically appearing mitochondrial cytopathy associated with large deletions of a variable proportion of mitochondrial DNA (mtDNA) molecules. Six patients with PEO-plus/KSS in whom muscle biopsy was performed following a complete clinical study are described. The muscle was processed by conventional histochemical techniques, electron microscopy, and genetic study (Southern transference, polymerase chain reaction, restriction cartography and both manual and automatic sequencing). The percentage of mutated mtDNA molecules for each patient was obtained by densitometry. The 6 patients presented multiorganic clinical manifestations characteristics of most mitochondrial diseases. The presence of destructured red fibers were observed in all the biopsies. All the patients presented a deletion in the mtDNA of a size between 4,861 to 7,437 base pairs (bp). All the deletions appeared flanked by direct repetitions from 4 to 13 bp and one also presented inverse repetitions from 5 to 6 bp in the zone next to the rupture point. In the 6 cases heteroplasmia was observed with a variable percentage of deleted molecules from 23 to 56%. The molecular basis of progressive external ophthalmoplegia-plus/Kearns-Sayre syndrome appears to be the existence of sole, large deletions in the mitochondrial DNA with the varying in location and percentage conditioning the appearance of different phenotypes similar among themselves. The 7,437 base pair deletion was the most frequently observed in the patients analyzed.

Adolescent↗
PubMed1995

The 9-bp deletion in region V of mitochondrial DNA: evidence of mutation recurrence.

A deletion of one of the two copies of a 9-bp direct repeat sequence (CCCCCTCTA) in region V of mitochondrial DNA has previously been used as a polymorphic anthropological marker for people of east Asian origin, and to a lesser extent, in Oceanian and African populations. We report the presence of the 9-bp deletion in homoplasmy in skeletal muscle fibers and lymphocytes of a Spanish Caucasian individual. Other mitochondrial DNA polymorphisms associated with the 9-bp deletion characteristic of other populations were not present. Our results suggest that the 9-bp deletion probably originated independently in the maternal lineage of the propositus, and that it can thus be described as a recurrent mutation.

Anthropology↗
PubMed1995

[Cerebral vascular complications in Conn's disease: report of two cases].

We report two patients with arterial hypertension (AHT) secondary to Conn's disease and cerebral vascular accident (CVA). Both had histories of long-standing AHT that had been poorly controlled with drugs, though no complications had developed up to the time of presentation. One CVA was a hemorrhage in the right capsular-lenticular region and the other was a cerebral ischemic infarction. Blood tests done upon admission found low potassium levels. The final clinical-pathological diagnosis was primary hyperaldosteronism secondary to suprarenal adenoma. After laparoscopic surgery AHT reverted to normal in one patient. Although Conn's disease is a rare cause of AHT, early diagnosis and treatment can provide a cure and prevent the development of severe complications.

Adenoma↗
PubMed1994

Multiple deletions of mtDNA in two brothers with sideroblastic anemia and mitochondrial myopathy and in their asymptomatic mother.

Two brothers presented with a clinical picture characterized by sideroblastic anemia, mild pancreatic insufficiency and progressive muscle weakness. The presence of an associated permanent basal lactic acidemia raised the suspicion of a mitochondrial disease. A muscle biopsy performed in both siblings proved the presence of a significant number of ragged-red fibers, and respiratory chain enzymatic determinations demonstrated a reduced activity of complexes I, III and IV. Mitochondrial DNA studies disclosed the presence of multiple deletions both in skeletal muscle and, to a lesser extent, in leukocytes. Similar, but not identical deletions were also present in the leukocytes and muscle from their mother. Deletions were flanked by short direct repeats. We conclude that such patients suffer from a familial form of mitochondrial disease clinically resembling Pearson's syndrome, with a probably autosomal dominant inheritance.

Adult↗
PubMed1994

Idiopathic pulmonary-renal syndrome with antiproteinase 3 antibodies.

In this report, we describe a patient who developed acute renal failure and fatal pulmonary hemorrhage. Autopsy examination revealed pauci-immune necrotizing glomerulonephritis and pauci-immune hemorrhagic alveolar capillaritis. No evidence of granulomatous inflammation or vasculitis other than capillaritis was found in either lungs or kidneys. In addition, histopathologic examination of the upper respiratory tract, liver, spleen, digestive tract, and skeletal muscle was completely normal. The patient's serum sample disclosed antiproteinase 3 antibodies with an immunofluorescence titer of 1:1,600. Although there have been reports of patients with pulmonary-renal syndrome in association with antiproteinase 3 antibodies in the absence of a well-known vasculitic disease, we have not so far seen a case documented by a detailed autopsy study such as is presented here. In view of our findings and those of some other reports on this clinicopathologic condition, we suggest that this might represent a distinct form of vasculitis with exclusive capillary involvement.

Aged↗
PubMed1993

Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease.

Different abnormalities in mitochondrial electron transport chain activity have been demonstrated in muscle and other tissues of patients with idiopathic Parkinson's disease (PD). We studied eight Spanish patients with PD to evaluate the functional activity of the electron transport chain in muscle mitochondria from patients of this country. We found lower complex I activity (nmol.min-1.mg-1) in patients (245.8 +/- 42.8) than in controls (331.6 +/- 60.1) (p = 0.004) and lower complex IV activity in patients (46.1 +/- 9) than in controls (144.1 +/- 42.3) (p = 0.00001). Complex V activity was also decreased in two patients and complex II and III activities were normal in all of them. Although these results strongly suggest an alteration in mitochondrial DNA in PD, the various electron transport chain defects in different tissues seem to be nonspecific.

Aged↗