Apolipoprotein J deficiency in types I and IV carbohydrate-deficient glycoprotein syndrome (glycanosis CDG)
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Child↗
Biomedical subjects
S Weidinger
Publications and source records attributed to S Weidinger.
[Detection of tyrosinase mRNA using reverse transcription/polymerase chain reaction with fine needle punctures of melanoma metastases].
Tyrosinase mRNA produced by melanoma cells can be detected by reverse transcriptase-polymerase chain reaction (rt-pcr) with fine-needle tissue punctures. Fine-needle punctures from six suspected skin and lymph node metastases in three patients with malignant melanoma were analysed via rt-pcr for tyrosinase mRNA. All the suspected metastases were surgically removed and histologically examined separately. In each case the rt-pcr results and the histological diagnosis corresponded. This less invasive and highly sensitive method could prove to be a useful alternative in the diagnosis of melanoma metastasis.
Aged↗
Allotypes of alpha 1-antitrypsin in patients with cystic fibrosis, homozygous and heterozygous for deltaF508.
In cystic fibrosis (CF) neutrophil released serine proteinase activity may facilitate Pseudomonas aeruginosa lung colonization, leading to chronic infection. Since such activity is mostly controlled by alpha 1-antitrypsin (alpha 1-AT), we postulated that with CF carrying deficient alpha 1-AT variants might be at higher risk for P. aeruginosa acquisition and might reveal other phenomena, specific for serine proteinase activity. In 215 Danish patients with CF, homozygous (80%) or heterozygous (20%) for the major CF mutation deltaF508, alpha 1-AT variants were determined. Carriage of deficient alpha 1-AT variants was correlated to an earlier onset of P. aeruginosa lung infection (P < 0.0001), higher total IgG (P < 0.0001), and P. aeruginosa-specific serum antibodies (P < 0.0001). The two groups did not differ in lung function, probably due to intensive antimicrobial treatment.
Adolescent↗
High-dose intravenous melphalan in a patient with multiple myeloma and oliguric renal failure.
A kappa light-chain myeloma was diagnosed as the underlying disease in a 52-year-old woman with acute oliguric renal failure. The patient was erroneously treated with high-dose intravenous melphalan (60 mg/m2). Because of this overdose treatment with granulocyte colony-stimulating factor was initiated, but pronounced absolute leukopenia (white blood cell count < 0.5 x 10(9)/l) developed and lasted for 13 days. Following melphalan treatment a continuous increase in urine volume was accompanied by a decrease of serum creatinine and blood urea nitrogen. Within 10 days after the administration of melphalan the patient no longer required hemodialysis. We conclude that high-dose chemotherapy in combination with hematopoietic growth factors should be considered in individual cases with newly diagnosed light-chain nephropathy.
Acute Kidney Injury↗
Hypothyroidism phenocopy in glycanosis CDG (carbohydrate-deficient glycoprotein syndrome)
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Carbohydrate Metabolism, Inborn Errors↗
Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele.
We have investigated the molecular basis of 15 new alpha 1-antitrypsin (alpha 1AT) variants. Phenotyping by isoelectric focusing (IEF) was used as a screening method to detect alpha 1AT variants at the protein level. Genotyping was then performed by sequence analysis of all coding exons, exon-intron junctions, and the hepatocyte-specific promoter region including exon Ic. Three of these rare variants are alleles of clinical relevance, associated with undetectable or very low serum levels of alpha 1AT:the PI*Q0saarbruecken allele generated by a 1-bp C-nucleotide insertion within a stretch of seven cytosines spanning residues 360-362, resulting in a 3' frameshift and the acquisition of a stop codon at residue 376; a point mutation in the PI*Q0lisbon allele, resulting in a single amino acid substitution Thr68(ACC)-->Ile(ATC); and an in-frame trinucleotide deletion delta Phe51 (TTC) in the highly deficient PI*Mpalermo allele. The remaining 12 alleles are associated with normal alpha 1AT serum levels and are characterized by point mutations causing single amino acid substitutions in all but one case. This exception is a silent mutation, which does not affect the amino acid sequence. The limitation of IEF compared with DNA sequence analysis, for identification of new variants, their generation by mutagenesis, and the clinical relevance of the three deficiency alleles are discussed.
Alleles↗
A leucine-to-proline substitution causes a defective alpha 1-antichymotrypsin allele associated with familial obstructive lung disease.
Using denaturing gradient gel electrophoresis and direct sequencing of amplified genomic DNA, we have identified two defective mutants of the human alpha 1-antichymotrypsin (ACT) gene associated with chronic obstructive pulmonary disease (COPD). A leucine 55-to-proline substitution causing a defective ACT allele (Bochum-1) was observed in a family with COPD in three subsequent generations. Another mutation, proline 229-to-alanine (Bonn-1), was associated with ACT serum deficiency in four patients with a positive family history. These mutations were not detected among 100 healthy control subjects, suggesting a possible pathogenetic role of ACT gene defects in a subset of patients with COPD.
Amino Acid Sequence↗
Orosomucoid system: 17 additional orosomucoid variants and proposal for a new nomenclature.
There are two forms of orosomucoid (ORM) in the sera of most individuals. They are encoded by two separate but closely linked loci, ORM1 and ORM2. A number of variants have been identified in various populations. Duplication and nonexpression are also observed in some populations. Thus, the ORM system is very complicated and its nomenclature is very confusing. In order to propose a new nomenclature, ORM variants detected by several laboratories have been compared and characterized by isoelectric focusing (IEF) followed by immunoprinting. A total of 57 different alleles including 17 new ones were identified. The 27 alleles were assigned to the ORM1 locus, and the others to the ORM2 locus. The designations ORM*F1, ORM1*F2, ORM1*S and ORM2*M were adopted for the four common alleles instead of ORM1*1, ORM1*3, ORM1*2 and ORM2*1 (ORM2*A), respectively. The variants were designated alpha numerically according to their relative mobilities after IEF in a pH gradient of 4.5-5.4 with Triton X-100 and glycerol. For the duplicated genes a prefix is added to a combined name of two alleles, e.g. ORM1*dB9S. Silent alleles were named ORM1*Q0 and ORM2*Q0 conventionally. In addition, the effects of diseases to ORM band patterns after IEF are also discussed.
Alleles↗
Genetic polymorphism in the Garfagnana population (Tuscany).
Blood group systems ABO, KEL, MN, RH, secretor status for ABH blood group substances, red cell enzymes ACP1, ESD, AK1, 6-PGD, PGM1 subtypes, serum markers GC, TF, PI, AHSG, ORM1 and chromosomal heteromorphism Q, C, DA/DAPI were examined in a population sample of the Garfagnana, a semi-isolated mountainous area in the province of Lucca (Tuscany, Italy). The total sample was subdivided and analysed according to the more recent historical events which have occurred in Garfagnana. The observed phenotype and gene frequencies were discussed in the context of other population samples from the same province and of the same region. As a whole, the results concur in pointing out a certain degree of heterogeneity within the area and a high differentiation from the rest of Tuscany. Such peculiar genetic features of the population have to be related to the historical, geographic and cultural isolation of the Garfagnana.
Blood Group Antigens↗
Mis-sense mutation of alpha 1-antichymotrypsin gene associated with chronic lung disease.
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Base Sequence↗
Reliable phenotyping of alpha-1-antitrypsin by hybrid isoelectric focusing in an ultranarrow immobilized pH gradient.
Genetically determined phenotypes of the highly polymorphic human alpha 1-antitrypsin were examined by hybrid isoelectric focusing in a narrow immobilized pH gradient. The chosen pH range from 4.45 to 4.75 was useful for identification and classification of the common PI M subtypes and a number of PI variants in the microheterogeneous regions of m6, m7, and m8. A high degree of resolution and an improved sharpness of PI bands was achieved with this excellent technique. It allowed the distinction of a new PI M variant, which has been designated M8, or Mingolstadt, according to the PI nomenclature. The pI difference of this mutant to the slightly cathodically located subtype M3 is approximately 0.001 pH unit. In addition, some common as well as rare phenotypes are presented.
Hydrogen-Ion Concentration↗
PGD Port Elizabeth: a new variant found in South Africa.
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Genetic Variation↗
What is Pi (proteinase inhibitor) null or PiQO?: a problem highlighted by the alpha 1 antitrypsin Mheerlen mutation.
alpha 1 antitrypsin deficiency is associated with predisposition to the development of pulmonary emphysema and childhood cirrhosis. There are two common deficiency alleles in the European population, proteinase inhibitor (Pi) Z and S. In addition, there are rare Pinull or QO variants which can be difficult to diagnose. A family assigned as having the PiQO allele by AAT protein quantification and isoelectric focusing was shown by DNA sequencing to have the PiMheerlen mutation (Pro369-Leu). This highlights the difficulties of diagnosis of PiQO.
Alleles↗
[Diagnosis and nosology of glycanosis CDG ("carbohydrate deficient glycoprotein syndrome")].
BACKGROUND: The "Carbohydrate-deficient glycoprotein syndrome" is a recently discovered inborn error of complex carbohydrate metabolism. The disease involves a number of organ systems and various deficient glycoproteins. An abnormal isoform of serum transferrin is of diagnostic value. METHODS: We analysed the glycoprotein alpha-1-antitrypsin of two affected infants and their clinically healthy parents using high resolution isoelectric focusing technique. Besides normal isoforms of alpha-1-antitrypsin, we found an abnormal cathodic isoform ("CDG-alpha-1-antitrypsin") which represented almost half of the total amount of alpha-1-antitrypsin of the patients. RESULTS: This new marker-glycoprotein suggests a defect of the production of biantennary and of triantennary N-glycans during an early step of their synthesis, resulting in monoantennary N-glycans. Also this marker-glycoprotein seems to be a specific biochemical diagnostic tool for discovering glycanosis CDG (Carbohydrate-deficient glycoprotein syndrome). The mode of inheritance is probably incomplete autosomal dominant. The same genetic defect of N-glycan synthesis may be present in more than one type of the hybrid molecule glycoprotein, and was also found in transferrin, resembling a "genetic back-pack", that might explain the multitude of clinical symptoms. CONCLUSION: In view of these findings, we present novel systematics of those diseases that are due to inborn errors of N-glycan synthesis, and which we suggest to call "glycanoses".
Abnormalities, Multiple↗
[Alcoholic ketoacidosis--3 episodes in one patient].
3 episodes of alcoholic ketoacidosis were observed in one female patient over a period of 19 months. The clinical picture consisted of vomiting, dehydration, hyperventilation and abdominal pain. Predominant laboratory findings were acidosis (pH less than 7) and hyperglycaemia, with blood glucose values of 354, 330 and 147 mg/dl. This disorder is an important cause of metabolic acidosis, but especially in the German literature there are only rare reports on this issue. The picture of ketoacidosis in mostly chronically malnourished alcoholics reflects not only the complex abnormalities of acid-base balance caused by excessive cumulation of ketoacids, but also the related severe depletion of electrolytes and extracellular volume. Adequate acute therapy (as for diabetic ketoacidosis) and thorough follow-up treatment of any concurrent conditions result in rapid reversal of the syndrome in most cases. Since there are few reports of repeated episodes in one patient, an overview of this disorder is presented concerning management and differential diagnosis of the basis of our case report.
Acidosis↗
Description of a new variant in the glutamate-oxaloacetate transaminase system by thin-layer agarose gel isoelectric focusing.
Thin-layer isoelectric focusing in agarose within the pH range of 4.0-6.5 has shown a high resolution of the soluble cytoplasmic glutamate-oxaloacetate transaminase (GOT1) banding pattern. The complex pattern of the common GOT1 phenotype consists of eight bands with different intensities. A genetic variant of GOT1, which has been designated GOT1 Mexico, could tentatively be identified.
Alleles↗
DNA polymorphisms associated with a new alpha 1-antitrypsin PIQ0 variant (PIQ0riedenburg).
A new PIQ0 variant (PIQ0riedenburg) is described; it is caused by a complete deletion of the alpha 1-antitrypsin (alpha 1 AT) gene. The deletion gives rise to four new restriction fragment length polymorphisms (RFLPs) detected with a genomic probe of the 5' region of the gene. Analysis of the RFLPs indicates that the deletion starts immediately upstream of exon Ic. The deletion extends into the 3' flanking region of the gene but does not include the alpha 1 AT-related gene (the PIL gene), which is located 12 kb downstream of the alpha 1 AT gene.
Alleles↗
New mutation versus exclusion at the alpha-1-antitrypsin locus: a multifaceted approach in a problematical paternity case.
In a case of disputed paternity with overwhelming indications of fatherhood for the putative father, as supported by serological tests and biostatistical evaluation, a classical exclusion constellation was found at the alpha 1-antitrypsin (PI) locus: mother PI M1; child PI M1M3, and putative father PI M1M2. Additional studies included PI oligonucleotide phenotyping and DNA fingerprint analysis. Results from the entire data set led us to assume a rare genetic event at the paternal PI locus. Intracistronal crossing-over offered the most parsimonious explanation, and was compatible with the PI gene DNA sequence and the amino acid sequences of the molecule and its allelic forms, as well as with the experimental findings.
Adult↗