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N Zöllner

Publications and source records attributed to N Zöllner.

At least 19 recordsLinked to original sources
PubMed1992

Molecular basis of AMP deaminase deficiency in skeletal muscle.

AMP deaminase (AMPD; EC 3.5.4.6) is encoded by a multigene family in mammals. The AMPD1 gene is expressed at high levels in skeletal muscle, where this enzyme is thought to play an important role in energy metabolism. Deficiency of AMPD activity in skeletal muscle is associated with symptoms of a metabolic myopathy. Eleven unrelated individuals with AMPD deficiency were studied, and each was shown to be homozygous for a mutant allele characterized by a C----T transition at nucleotide 34 (codon 12 in exon 2) and at nucleotide 143 (codon 48 in exon 3). The C----T transition at codon 12 results in a nonsense mutation predicting a severely truncated AMPD peptide. Consistent with this prediction, no immunoreactive AMPD1 peptide is detectable in skeletal muscle of these patients. This mutant allele is found in 12% of Caucasians and 19% of African-Americans, whereas none of the 106 Japanese subjects surveyed has this mutant allele. We conclude from these studies that this mutant allele is present at a sufficiently high frequency to account for the 2% reported incidence of AMPD deficiency in muscle biopsies. The restricted distribution and high frequency of this doubly mutated allele suggest it arose in a remote ancestor of individuals of Western European descent.

AMP Deaminase↗
PubMed1992

Familial synovial chondromatosis combined with dwarfism.

In a family with synovial chondromatosis affecting at least three, presumably five members, the articular disorder was combined with dwarfism. The persons with joint disorders were below the third percentile in body height, but family members with normal articular function had normal height. We believe this to be the first description of a combination of synovial chondromatosis with genetically caused dwarfism.

Adolescent↗
PubMed1992

Familial defective apolipoprotein B-100: a common cause of primary hypercholesterolemia.

Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder characterized by a decreased binding of low density lipoprotein (LDL) to the LDL receptor due to defective apo B-100. FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. The arginine (3500)----glutamine mutation has been observed in several populations in North America and Europe with a similar frequency of approximately 1/500 to 1/700. Haplotype analysis has demonstrated that the arginine(3500)----glutamine mutation occurs on the same chromosomal background. The fact that all individuals with FDB are of Caucasian extraction implies that the mutation has its origin in this population. The arginine(3500)----glutamine mutation has a profound impact of varying strength on the plasma LDL cholesterol level, leading to heterogeneous clinical expression comparable to "classic" familial hypercholesterolemia (FH) caused by a defective LDL receptor: tendon xanthoma, premature atherosclerosis and arcus lipoides. The present data suggest that the combination of these clinical features is no longer appropriate for the diagnosis of LDL-receptor-defective FH, but may be a common feature of a defective LDL receptor pathway originating either from defective LDL receptors or from malfunctioning ligand apo B-100.

Apolipoprotein B-100↗
PubMed1992

Allele-specific and asymmetric polymerase chain reaction amplification in combination: a one step polymerase chain reaction protocol for rapid diagnosis of familial defective apolipoprotein B-100.

We have combined the asymmetric polymerase chain reaction (PCR) with allele-specific PCR to detect a single point mutation. A set of two priming oligonucleotides and a third allele-specific primer were used to identify heterozygotes for a G to A mutation at nucleotide 10,708 in the apolipoprotein B (apo B) gene. The system requires neither restriction enzyme digestion nor allele-specific oligonucleotides as conventionally applied for allele-specific hybridization of slot blots. This method clearly allows for the detection of the mutant allele by inspection, after agarose gel electrophoresis of a single PCR reaction. DNA from 40 patients with familial defective apo B-100 due to the G to A mutation at nucleotide 10,708 in the apo B gene and their normal relatives was analyzed. Complete agreement with allele-specific hybridization of slot blots confirms supposition that the system is effective to screen a larger population.

Alleles↗
PubMed1992

Familial defective apolipoprotein B100: clinical characteristics of 54 cases.

Familial defective apolipoprotein B100 (FDB) is a recently identified dominantly inherited genetic disorder, which is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor. FDB is caused by a G to A mutation at nucleotide 10 708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To determine the consequences of the arginine(3500)----glutamine mutation on plasma lipid levels and other clinical features, we have investigated 54 FDB heterozygotes from Germany (24 men, 30 women, mean age 37.2 (4-73) years). The average total cholesterol level in plasma was 308 mg/dl (average LDL-cholesterol 242 mg/dl), which was 116 mg/dl (120 mg/dl) above the 50th percentile of the age and sex-matched controls reported in the LRC population studies (Lipid Research Clinics' Program 1980). Tendon xanthoma and arcus lipoides were present in 25.9% and 22.2% of the patients, respectively. Plaques in the carotid arteries, determined by duplex scanning, were present in 38.9%, and coronary artery disease was present in 22.2%. This study shows that the combination of tendon xanthoma, arcus lipoides and premature atherosclerosis is no longer totally appropriate for the diagnosis of familial hypercholesterolemia (FH). It rather seems that these features are characteristic of a defective LDL receptor pathway, which could be caused by a defective LDL receptor or a defective ligand apo B100. The distinction between FH and FDB may have therapeutic implications, because certain lipid lowering drugs act by stimulation of the LDL receptor, which has a normal function in FDB.

Adolescent↗
PubMed1992

Effects of hypercholesterolemia on the nucleotide content in human blood cells.

In hypercholesterolemia significant changes in the nucleotide pattern of erythrocytes and lymphocytes as determined by high performance liquid chromatography were found. The decrease in ATP of lymphocytes in hypercholesterolemia from 10.4 +/- 0.3 to 7.0 +/- 0.4 nmol mg-1 protein (n = 8) was associated with an increase in ADP from 2.2 +/- 0.2 to 4.0 +/- 0.2 nmol mg-1 protein (P less than 0.005). The pattern of guanosine phosphates likewise was found to be changed in hypercholesterolemia. Akin to lymphocytes, red blood cells displayed marked changes in nucleotide levels. No such changes were observed in platelets. Cultured lymphocytes incubated with human plasma low density lipoproteins (LDL) (140 mg cholesterol dl-1) displayed a reversible fall in ATP and an increase in ADP by about 40% and 160%, respectively, with high density lipoproteins (HDL) or very low density lipoproteins (VLDL) being essentially ineffectual. It is concluded that in hypercholesterolemia a significant change in the nucleotide pattern of blood cells is exerted by the increase in LDL. Possible pathophysiological implications are discussed.

Adolescent↗
PubMed1992

Diagnosis of familial hypercholesterolemia using DNA haplotype analysis in three large families with two hyperlipidemic parents.

Since the cloning of the human LDL receptor (LDLR) gene, familial hypercholesterolemia (FH) can be diagnosed by recombinant DNA technology either using restriction enzyme mapping to detect major rearrangements of the gene or using restriction fragment length polymorphisms (RFLPs) and linkage analysis in family studies. Genotypes and haplotypes of four RFLPs (StuI, ApaII 5', PvuII, NcoI) were used to study the inheritance of the detective LDLR gene in three families. Diagnosis of FH based on the lipid levels alone was not possible because in these kindreds both parents exhibit elevated lipid levels. However, in two families using haplotype analysis, elevated cholesterol levels in certain relatives could be attributed to the inheritance of a defective LDRL gene and thereby distinguished from hypercholesterolemia due to familial combined hyperlipidemia. In the third family where both hypercholesterolemic parents carried a defective LDLR gene, a case of homozygous FH could be excluded in a child by demonstrating the inheritance of a normal LDLR gene.

Adult↗
PubMed1992

[Erythema nodosum].

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Identification of a 76-year-old patient with compound heterozygous familial hypercholesterolemia by haplotype analysis of the LDL receptor gene.

In a large family with clinical characteristics of heterozygous familial hypercholesterolemia (FH) seven restriction fragment length polymorphisms (RFLP) were used to determine low-density-lipoprotein receptor (LDLR) gene haplotypes. Following the inheritance of the LDL receptor genes characterized by their seven RFLP haplotypes, two different alleles were found to cosegregate with elevated cholesterol levels within this family. In a 76-year-old man both alleles identified as defective were present, thus classifying this individual as heterozygous compound for FH. In five heterozygous family members one allele was associated with 38% higher cholesterol levels when compared to the other mutant allele in two heterozygous family members. Cosegregation of hypercholesterolemia with the apolipoprotein B (apoB) gene and apolipoprotein E (apoE) gene was excluded by genotyping all individuals for the apoB XbaI RFLP and apoE polymorphisms. These findings are consistent with variable phenotypic expression of the mutant LDLR gene alleles.

Aged↗
PubMed1991

The spontaneous course of small abdominal aortic aneurysms. Aneurysmal growth rates and life expectancy.

Since abdominal ultrasonography has become a routine diagnostic procedure, increasing numbers of small asymptomatic abdominal aortic aneurysms are detected incidentally. Of 128 patients (108 male, 20 female) with abdominal aortic aneurysms, 96 patients were observed clinically and by repeated ultrasound studies for an average of 3.47 years, adding up to a total observation period of 333 patient-years. Among these 96 patients, 72 had small aneurysms (averaged diameters less than 5 cm). Three of them were lost to follow up. None of the remaining 69 patients died from rupture, 20 died from other causes and 8 patients were successfully operated. Of the patients with a large aneurysm one was lost to follow up. Five patients of the remaining 23 died as a result of rupture, 7 were successfully operated. The average growth rate of small aneurysms was 0.18 cm/year, whereas the larger aneurysms showed a growth rate of 0.28 cm/year (diameter). The survival rate of patients with small aneurysms was 94% after one year, 80% after 3 years, and 73% after 5 years, indicating that life expectancy is reduced in patients with an aneurysm of the abdominal aorta, but not because of complications of the aneurysm.

Adult↗
PubMed1991

Effects of human low-density lipoproteins on the nucleotide patterns of cultured pig aortic endothelial cells.

Cultured pig aortic endothelial cells display significant changes in their nucleotide patterns after incubation with LDL-cholesterol purified from normal human plasma as determined by HPLC. Incubation at 70 mg/dl LDL-cholesterol for 24 h at 37 degrees C caused a significant decrease (P less than 0.001) in ATP from a control value of 14.0 +/- 0.4 nmol/mg protein to 6.6 +/- 0.9 nmol/mg protein (n = 4) with a concomitant increase in ADP and AMP. At higher LDL concentrations these effects were even more pronounced but still reversible. Akin to adenine nucleotides, the guanosine and uridine phosphates as determined by HPLC were changed. In contrast to LDL, HDL and VLDL were ineffectual.

Animals↗
PubMed1991

Identification of a silent point mutation in the LDL-receptor gene by direct DNA sequencing.

To study the allelic variation at the human LDL-receptor gene locus in a number of individuals with familial hypercholesterolemia, a protocol was applied for direct sequence analysis of genomic DNA. The asymmetric polymerase chain reaction (PCR) was used to synthesize single-stranded DNA. Sequencing was carried out with modified T7 DNA polymerase (Sequenase version 2.0, United States Biochemical) after purification of the amplification product with a glass powder adhesion method. The method is sensitive enough to identify the heterozygous state of allelic variation and bypasses cumbersome cloning and subcloning procedures. Here we report the occurrence of a guaninine-to-adenine change in the codon for amino acid 655. However, the glycine residue is not replaced by the base change at this position, and the mutation observed here does not represent the underlying genetic defect of the LDL-receptor defect in this individual. Preliminary data suggest that this mutation represents a rare genetic variation.

Amino Acid Sequence↗