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U G Froster

Publications and source records attributed to U G Froster.

At least 19 recordsLinked to original sources
PubMed2005

[Hereditary multiple exostoses. Molecular genetic analysis of the EXT1 gene in an unusual family].

Hereditary multiple exostosis (HME), a disorder inherited in an autosomal dominant manner, is characterized by multiple projections of bone, mainly at the extremities. The risk of malignant transformation of the exostoses is estimated to be up to 2%. The most common underlying cause of the disease involves mutations in either the EXT1 or the EXT2 gene. We report on the clinical and molecular findings in a family affected with HME.A mother and her three children from different partnerships, all clinically diagnosed with HME, were referred for genetic counseling. Subsequently, molecular analysis of the EXT1 gene was performed according to standard procedures. We identified a mutation in the EXT1 gene in all four affected family members (delA in codon 133). This mutation has not been previously described and is suggested to cause the disease in this family. Identification of disease causing mutations in patients with HME and their relatives can help to improve the clinical management of tumor prevention, early tumor detection, and orthopedic therapy.

Adolescent↗
PubMed2004

Another case of autosomal dominant exstrophy of the bladder.

OBJECTIVE: Exstrophy of the bladder is a rare malformation due to an anterior midline defect. Most cases of this condition with variable expression occur sporadically, but there are some cases indicative of a strong genetic component apart from environmental factors. This is a report about another rare mother-child pair with bladder exstrophy. METHODS: We present the clinical data of a familial case of bladder exstrophy with an affected mother and her equally affected male fetus. RESULTS: Prenatal diagnosis of bladder exstrophy in the fetus was assessed by ultrasound at the 19th gestational week and was confirmed after termination of pregnancy at the 21st gestational week. CONCLUSION: The present case may be additional evidence for an autosomal dominant inherited variant of this malformation complex with implication for counselling of affected patients.

Abortion, Induced↗
PubMed2003

[Molecular genetic mutation analysis of the PTPN11 gene in the multiple lentigines (LEOPARD) syndrome].

BACKGROUND AND OBJECTIVE: LEOPARD syndrome (MIM #151100) is a rare autosomal dominant condition with characteristic skin anomalies, facial dysmorphism, hypertelorism, cardiac anomalies, and occasional conductive hearing loss. Mutations in the PTPN11 gene are described as the causal gene defect for the clinical features of Noonan syndrome (MIM #163950), but also for LEOPARD syndrome. For confirmation of the clinical diagnosis of multiple lentigines syndrome, the molecular genetic mutation analysis in the PTPN11 gene could be helpful. PATIENTS/METHODS: We report on a family with LEOPARD syndrome in which the mutation analysis in the father and his daughter in the PTPN11 gene was carried out us:ng PCR, DHPLC, and automated sequencing. RESULTS: We could identify both father and daughter as carriers of the mutation Y279C in the PTPN11 gene, which is known as a disease-related mutation. CONCLUSIONS: The allelic affinity to Noonan syndrome could thus be further supported.

Alleles↗
PubMed2003

Partial trisomy 22 resulting from rearrangements between chromosomes 11/22 and 16/22: a report of two cases.

UNLABELLED: Two male infants with partial trisomy 22 resulting from a rearrangement between chromosomes 11/22 and 16/22 were admitted to the Children's Hospital of the University of Leipzig within the space of two months. The characteristic phenotype of the infants is described and compared with the data on liveborn infants with trisomy 22, as reported in the literature. One of the infants reported here showed a prenatally detected hygroma colli. To the best of our knowledge this is the first description of a hygroma colli in this chromosomal disorder. CONCLUSION: Infants with trisomy 22 can present with variable phenotypes. It is important to bear the phenotype of chromosome 22 infants in mind.

Abnormalities, Multiple↗
PubMed2002

Characterization of chromosomal aberrations in a case of glioblastoma multiforme combining cytogenetic and molecular cytogenetic techniques.

A case of glioblastoma multiforme (GBM) that was investigated with a broad spectrum of cytogenetic and molecular cytogenetic techniques is reported. The results of cytogenetic studies, interphase fluorescence in situ hybridization, comparative genomic hybridization, and spectral karyotyping (SKY) are reported. Various structural chromosomal aberrations were identified, among which aberrations involving chromosome arm 2p were especially frequent. Using SKY, six translocations not previously described in GBM are reported.

Aged↗
PubMed2002

[Current aspects of the diagnosis of malignant hyperthermia].

OBJECTIVES: The aim of this work was to give a survey of experiences and results obtained over a period of 15 years of diagnosis of malignant hyperthermia in the MH centre in Leipzig. The new branch of MH diagnosis, the molecular genetics and its general diagnostic potential will be presented in more detail. METHODS: The in vitro contracture test (IVCT), which has been used in our department since 1986, represents the standard method for determining disposition to MH and in addition, suspected MH events were analysed by the clinical grading scale (CGS). In 1999, the diagnosis of MH in our centre was supplemented by molecular genetic examination of the skeletal ryanodine receptor gene (RYR1). RESULTS: A total of 1,456 muscle tests (IVCT) in patients with a potential MH disposition, provided 376 MH susceptible (MHS), 121 MH equivocal (MHE) and 921 MH negative (MHN) results. Out of these 309 persons had a previous clinical MH event, but for the majority of these persons a real MH disposition could be excluded by the IVCT (197 MHN). In 99 independent MH families, the RYR1 was genetically screened identifying a mutation in 46, whereby 18 different RYR1 point mutations were found of which 4 (Arg401Cys, Ile2182Phe, Gly2375Ala, Ile2453Thr) have not yet been published. CONCLUSIONS: The disposition to MH may be assessed by the IVCT, DNA analysis and with limitations by the clinical phenotype. The IVCT represents a highly specific method, the DNA analysis appears to be very specific. Under defined conditions an alternative use of the methods is possible. However, these methods should not be regarded as in competition but rather their potential should be complementary or used in specific situations in order to avoid non-detection of MH events in affected families.

Anesthetics↗
PubMed2002

Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations.

BACKGROUND: The ryanodine receptor of the skeletal muscle (RYR1) seems to be of outstanding importance in the pathogenesis of malignant hyperthermia (MH). It has been shown that point mutations in the RYR1 gene are strongly associated with the MH phenotype. A correctly determined phenotype is the basic prerequisite for adequate genetic MH screening. In this study we examined only those MH susceptible patients for the presence of potential RYR1 mutations who showed strong pathological muscle responses in the in vitro contracture test (IVCT). METHODS: A total of 56 MHS index patients who complied with the following IVCT criteria were included in the molecular genetic investigation: Contracture forces > or =4 mN at a caffeine concentration of 2.0 mmol/l and > or =8 mN at a halothane concentration of 0.44 mmol/l. DNA sequences of exons 2, 6, 9, 11, 12, 14, 15, 17, 39, 40, 45, 46, 102 of the RYR1 gene were analysed by the direct sequencing technique. Furthermore, if an MH mutation was identified in an index patient, all relatives were screened for their family specific RYR1 defect. RESULTS: In 39 index patients an RYR1 mutation was detected: Arg163Cys (n = 2), Asp166Asn (n = 1), Gly341Arg (n = 2), Arg401His (n = 2), Arg614Cys (n = 12), Asp2129Glu (n = 1),Vol2168Met (n = 1), Thr2206Met (n = 9), Ala2428Thr (n = 1), Gly2434Arg (n = 2), Arg2435His (n = 1), Arg2452Trp (n = 1), Arg2454His (n = 4). Three new RYR1 mutations were identified. We found a potential MH mutation in a further 130 relatives of the 39 index patients. Thirty-seven individuals were classified as MHS exclusively by molecular genetic techniques and did not have to undergo the IVCT. CONCLUSIONS: The ascertained high rate of successful MH mutation screening (69.64%) is obviously associated with the more clearly defined MHS diagnosis in the IVCT. According to the EMHG guidelines for the molecular genetic detection of MH susceptibility, a positive MH disposition could be determined in numerous persons by a less invasive technique.

Anesthetics, Inhalation↗
PubMed2001

Mosaic chromosomal aberrations in synovial fibroblasts of patients with rheumatoid arthritis, osteoarthritis, and other inflammatory joint diseases.

Chromosomal aberrations were comparatively assessed in nuclei extracted from synovial tissue, primary-culture (P-0) synovial cells, and early-passage synovial fibroblasts (SFB; 98% enrichment; P-1, P-4 [passage 1, passage 4]) from patients with rheumatoid arthritis (RA; n = 21), osteoarthritis (OA; n = 24), and other rheumatic diseases. Peripheral blood lymphocytes (PBL) and skin fibroblasts (FB) (P-1, P-4) from the same patients, as well as SFB from normal joints and patients with joint trauma (JT) (n = 4), were used as controls. Analyses proceeded by standard GTG-banding and interphase centromere fluorescence in situ hybridization. Structural chromosomal aberrations were observed in SFB (P-1 or P-4) from 4 of 21 RA patients (19%), with involvement of chromosome 1 [e.g. del(1)(q12)] in 3 of 4 cases. In 10 of the 21 RA cases (48%), polysomy 7 was observed in P-1 SFB. In addition, aneusomies of chromosomes 4, 6, 8, 9, 12, 18, and Y were present. The percentage of polysomies was increased in P-4. Similar chromosomal aberrations were detected in SFB of OA and spondylarthropathy patients. No aberrations were detected in i) PBL or skin FB from the same patients (except for one OA patient with a karyotype 45,X[10]/46,XX[17] in PBL and variable polysomies in long-term culture skin FB); or ii) synovial tissue and/or P-1 SFB of normal joints or of patients with joint trauma. In conclusion, qualitatively comparable chromosomal aberrations were observed in synovial tissue and early-passage SFB of patients with RA, OA, and other inflammatory joint diseases. Thus, although of possible functional relevance for the pathologic role of SFB in RA, these alterations probably reflect a common response to chronic inflammatory stress in rheumatic diseases.

Arthritis, Psoriatic↗
PubMed2001

Maternal isochromosome 7q and paternal isochromosome 7p in a boy with growth retardation.

A 12-year 9-month-old boy with postnatal growth retardation, normal psychomotor development, and minor anomalies that included a triangular-shaped face, small nose, and narrow and high-arched palate is reported. The constitutional karyotype was 46,XY,i(7)(p10),i(7)(q10). Molecular investigations revealed the presence of a maternal isodisomy 7q and a paternal isodisomy 7p. The clinical and molecular findings are notably congruent with a recently reported case and support the hypothesis of one or more maternally imprinted genes located on the long arm of chromosomes 7 that regulate, in particular, postnatal growth.

Adolescent↗
PubMed2001

Determination of a positive malignant hyperthermia (MH) disposition without the in vitro contracture test in families carrying the RYR1 Arg614Cys mutation.

Molecular genetic methods are used with caution for determining positive malignant hyperthermia (MH) disposition in clinical MH diagnosis because of the genetic variability of this disease. But under defined conditions, genotyping can have an advantage over the standardized in vitro contracture test (IVCT) in respect of invasive approach, specificity, patient compliance, and the work and expense involved in the method. We aim to demonstrate this using 10 families with the Arg614Cys mutation in the ryanodine receptor as an example. Fifty-one index patients who had been classified as MH-susceptible (MHS) in the IVCT (European MH protocol) after a clinical MH incident or suspected MH were screened for the Arg614Cys (C1840-->T) mutation in the RYR1 gene because this mutation is more common in German MH families (9%). The family members of those index patients, in whom a Arg614Cys mutation was detectable, were also screened for the presence of this mutation (n=136), and the results were subjected to a more detailed analysis including existing IVCT findings (n=71). The Arg614Cys mutation was identified in a total of 64 members of the 10 independent families. In 35 individuals in this group, there was a definite concordance between the MHS diagnosis in the IVCT and the presence of the Arg614Cys mutation. No individual phenotyped as MH-negative carried the mutation. On the basis of the guidelines of the EMHG for molecular genetic detection of MH susceptibility, 29 individuals who bore the Arg614Cys mutation were classified as MHS without the IVCT. If a causal mutation is detected in an MH family, the MHS diagnosis can be deduced without the invasive IVCT in all other mutation carriers. Despite inclusion of only one (Arg614Cys) of all known MH mutations, the study emphasizes the practical use of a genetic approach for determination of a positive MH diagnosis.

Caffeine↗
PubMed2001

Homozygous and heterozygous Arg614Cys mutations (1840C-->T) in the ryanodine receptor gene co-segregate with malignant hyperthermia susceptibility in a German family.

The determination of susceptibility to malignant hyperthermia (MH) by genetic investigation is a controversial issue because of the genetic heterogeneity of this disorder. The requirement for such an approach in MH diagnosis is a strong correlation between MH-associated genetic abnormalities and phenotypic findings in the in vitro contracture test (IVCT). After a severe clinical MH crisis during general anaesthesia a patient was diagnosed by the IVCT in which susceptibility to MH was confirmed. Genetic screening for MH-related mutations in the RYR1 gene revealed the presence of a homozygous 1840C-->T base exchange (Arg614Cys substitution) in this patient. A specific search for this defect in 20 relatives led to the identification of a total of 11 Arg614Cys mutations. Of these, 10 were heterozygous (including both parents) and one was homozygous (sister). Further IVCTs were subsequently performed on the parents of the index patient, the homozygous sister and all relatives who did not carry the Arg614Cys in order to determine the genotype/phenotype correlation. After analysing these data, and because of the strong correlation between clinical, phenotypic, and genetic results in the index patient, we assigned the diagnosis 'MHS' to all the remaining Arg614Cys mutation carriers of that family without performing the IVCT.

Adult↗