Extremitätendefekte nach Chorionzottenanalyse im Kollektiv der Universitäts-Frauenklinik Lübeck

Ohne Zusammenfassung     

Tetrasomie 18p

Tetrasomy 18p is a rare chromosomal disorder. The phenotype results from the presence of a small extra metacentric marker chromosome, an isochromosome 18p. The syndrome is characterized by mild to moderate mental retardation, microcephaly, minor dysmorphic features and spasticity of the lower limbs. Here we report on a 2-year-old girl, who was referred because of developmental delay and minor dysmorphic signs. Cytogenetic investigations revealed a small supernumerary marker chromosome. Further analysis using spectral karyotyping (SKY?) and fluorescence in situ hybridization (FISH) identified the marker chromosome fragment as an isochromosome 18p.     

In-vitro-Kontrakturtest und Gentypisierung in der Maligne Hyperthermie-Diagnostik

BACKGROUND: Malignant hyperthermia (MH) is an autosomal dominantly inherited disorder, triggered in susceptible individuals by inhalation anesthetics and depolarizing muscle relaxants such as succinylcholine. Because of its high sensitivity (97-99%) and specificity (93.6%) as well as the genetic heterogeneity of MH disorder, the in vitro contracture test (IVCT) following the European-MH-Group is considered to be the "Gold Standard" for phenotypical determination of predisposed patients. On the other hand mutations in the skeletal muscle ryanodine receptor gene (RYR1) are tightly linked with MH susceptibility. After detecting a C1840T-mutation (Arg614Cys) in the RYR1 gene in one individual of a large MH family, we searched for this mutation in the remaining family members and determined the concordance with IVCT. METHODS: According to the European standard protocol for MH, 43 individuals of a large MH pedigree were assigned the status of MH susceptible (MHS),--negative (MHN) or--equivocal (MHE). The genetic investigation of 44 family members for the Arg614Cys-mutation was carried out by restriction fragment analysis: Genomic DNA was prepared from EDTA whole blood followed by amplification of a 918 bp RYR1 gene fragment by polymerase chain reaction. In presence of the Arg614Cys-mutation digestion with the restriction endonuclease Rsal would result in different DNA fragments of the amplified sequence than in absence of mutation. RESULTS: According to the response to IVCT, 25 individuals phenotypically revealed MHS, 7 MHE and 11 MHN status. Out of the 44 family members screened genetically for the Arg614Cys-mutation, the mutation was detected in 23 individuals. Out of them 19 were MHS and one was MHEc. The mutation was absent in 9 predisposed individuals, but six of them were MHE and three MHS. The mutation was also present in three individuals who had no MH screening (IVCT) before. For these last mentioned individuals the diagnosis MHS was deduced from genetic results. CONCLUSION: Based on results of IVCT the identification of a MH associated mutation in a MH-family can make and support a correct MH diagnosis and can resolve MHE findings.     

DHPLC mutation analysis of phenylketonuria

Denaturing high-performance liquid chromatography (DHPLC) is a sensitive and fast method for the detection of mutations which has been successfully used for mutation screening in several disease-related genes. Phenylketonuria (PKU, OMIM* 261600; McKusick 1986) is one of the most common autosomal recessive disorders in Europe. Mutations in the PAH gene mainly involve point mutations. In this study we report the successful use of DHPLC to analyse rapidly the complete coding sequence of the PAH gene in a total of 125 unrelated patients with PKU.     

VACTERL with hydrocephalus and branchial arch defects: Prenatal,clinical, and autopsy findings in two brothers

VACTERL association is defined as a combination of vertebral, anal, cardiac, tracheoesophageal, renal and limb anomalies, in particular radial defects. In recent years hydrocephalus was observed in patients with apparent VACTERL association. This particular condition was recognized as a hereditary entity with poor prognosis. Both autosomal recessive and X-linked forms were described. Here we report prenatal, clinical and autopsy findings in 2 brothers with this syndrome, who had, in addition, branchial arch anomalies. The recurrence in this family suggests X-linked inheritance. Branchial arch defects have so far not been described as part of the VACTERL + H syndrome. This observation further supports that a variety of brain anomalies including hydrocephalus associated with VACTERL anomalies represents separate entities with a considerable recurrence risk. The use of the term VACTERL “association” for these conditions is misleading and is discouraged. © 1996 Wiley-Liss, Inc.