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A Rauch

Publications and source records attributed to A Rauch.

At least 19 recordsLinked to original sources
PubMed2006

Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study.

Abacavir therapy is associated with significant drug hypersensitivity in approximately 8% of recipients, with retrospective studies indicating a strong genetic association with the HLA-B*5701 allele. In this prospective study, involving 260 abacavir-naive individuals (7.7% of whom were positive for HLA-B*5701), we confirm the usefulness of genetic risk stratification, with no cases of abacavir hypersensitivity among 148 HLA-B*5701-negative recipients.

Adult↗
PubMed2006

Dysphagia in elderly women: consider tetanus.

BACKGROUND: Dysphagia is seldom caused by tetanus; however, it is a common symptom of tetanus. Treating patients with tetanus is a rare event in industrialized countries and awareness is needed to recognize early signs of this serious disease. In Switzerland, the most recently reported tetanus cases occurred in elderly women with insufficient seroprotection. PATIENTS: We report on three elderly women presenting with dysphagia as an initial symptom of tetanus. RESULTS: Generalized tetanus was diagnosed in two patients upon admission, the third presented with cephalic tetanus with secondary generalization. All three patients had undetectable levels of tetanus antibodies and had no documented prior tetanus immunizations. Cultures of wound swabs grew Clostridium tetani in all cases. Electromyography was highly suggestive for tetanus in two patients. Treatment involved mechanical ventilation, intravenous benzodiazepine and metronidazole therapy, and active and passive tetanus immunization. The disease had a favorable outcome in two cases and was fatal in one. CONCLUSION: Tetanus remains a threat in patients with insufficient seroprotection and efforts are needed to improve tetanus immunization in these individuals. Tetanus should be considered in the differential diagnosis of dysphagia.

Aged↗
PubMed2005

Balanced translocation in a patient with craniosynostosis disrupts the SOX6 gene and an evolutionarily conserved non-transcribed region.

Craniosynostosis is a congenital developmental disorder involving premature fusion of cranial sutures, which results in an abnormal shape of the skull. Significant progress in understanding the molecular basis of this phenotype has been made for a small number of syndromic craniosynostosis forms. Nevertheless, in the majority of the approximately 100 craniosynostosis syndromes and in non-syndromic craniosynostosis the underlying gene defects and pathomechanisms are unknown. Here we report on a male infant presenting at birth with brachycephaly, proptosis, midfacial hypoplasia, and low set ears. Three dimensional cranial computer tomography showed fusion of the lambdoid sutures and distal part of the sagittal suture with a gaping anterior fontanelle. Mutations in the genes for FGFR2 and FGFR3 were excluded. Standard chromosome analysis revealed a de novo balanced translocation t(9;11)(q33;p15). The breakpoint on chromosome 11p15 disrupts the SOX6 gene, known to be involved in skeletal growth and differentiation processes. SOX6 mutation screening of another 104 craniosynostosis patients revealed one missense mutation leading to the exchange of a highly conserved amino acid (p.D68N) in a single patient and his reportedly healthy mother. The breakpoint on chromosome 9 is located in a region without any known or predicted genes but, interestingly, disrupts patches of evolutionarily highly conserved non-genic sequences and may thus led to dysregulation of flanking genes on chromosome 9 or 11 involved in skull vault development. The present case is one of the very rare reports of an apparently balanced translocation in a patient with syndromic craniosynostosis, and reveals novel candidate genes for craniosynostoses and cranial suture formation.

Amino Acid Sequence↗
PubMed2005

Genitourinary anomalies in Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B). Report of three Italian cases with hypospadias and review.

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1,000 male births. It is a complex disorder associated with genetic and environmental factors and can be part of genetic syndromes. Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation. It is caused by mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1). To date, 68 deletion/mutation-positive cases have been reported. Genitourinary anomalies are common in MWS. Here we report that hypospadias is common in males with this syndrome. In 39 patients where this information was available, hypospadias was present in 46% of patients (18/39). In the 3 Italian male cases reported here, hypospadias was always present. MWS should be considered by endocrinologists in patients with hypospadias associated with developmental delays/mental retardation, in particular in the presence of a distinct facial phenotype.

Child, Preschool↗
PubMed2005

Systematic assessment of atypical deletions reveals genotype-phenotype correlation in 22q11.2.

INTRODUCTION: Clinical variability associated with the common 22q11.2 microdeletion is well known, and has led to a broad application of FISH diagnostics with probes for loci TUPLE1 or D22S75 (N25), although, rarely reported atypical deletions associated with the same phenotypic spectrum would not be discovered by these probes. As most types of 22q11.2 deletions occur between low copy repeats within the region (LCR22), we assumed that atypical deletions should be more common than has been reported. To address this question and the possibility of a deletion size related genotype-phenotype correlation, we systematically assessed the frequency of typical and atypical 22q11.2 deletions in a large cohort of patients. METHODS: We used a set of 10 fluorescent in situ hybridisation (FISH) DNA probes, capable of detecting all reported and hypothetical deletions between the LCR22, and analysed 350 patients. Deletion sizes in atypical deletions were established by use of further FISH probes. Frequency of certain atypical deletions was analysed in controls by FISH and quantitative PCR. RESULTS: Patients with conotruncal heart defects (ctCHD) and with typical VCFS phenotype showed the common 3 Mb or nested 1.5 Mb deletions (in 18.5% and 78.6%, respectively), but no atypical deletion, while 5% (3/63) of patients with a mildly suggestive, atypical phenotype showed atypical distal deletions, which were not detected in patients with mental retardation of unknown origin or in healthy controls. DISCUSSION: These statistically significant differences demonstrate that atypical distal 22q11.2 deletions are very uncommon in patients with ctCHDs, while atypical congenital heart defects and mild dysmorphism are recognisable feature of atypical distal deletions. Further phenotype-genotype analysis disclosed association of significant developmental delay with the distal part of the common deletion region, and choanal atresia and atypical CHDs with the adjacent distal deletion region.

Chromosomes, Human, Pair 22↗
PubMed2005

Quantification of aortic valve area and left ventricular muscle mass in healthy subjects and patients with symptomatic aortic valve stenosis by MRI.

MRI allows visualization and planimetry of the aortic valve orifice and accurate determination of left ventricular muscle mass, which are important parameters in aortic stenosis. In contrast to invasive methods, MRI planimetry of the aortic valve area (AVA) is flow independent. AVA is usually indexed to body surface area. Left ventricular muscle mass is dependent on weight and height in healthy individuals. We studied AVA, left ventricular muscle mass (LMM) and ejection fraction (EF) in 100 healthy individuals and in patients with symptomatic aortic valve stenosis (AS). All were examined by MRI (1.5 Tesla Siemens Sonate) and the AVA was visualized in segmented 2D flash sequences and planimetry of the performed AVA was manually. The aortic valve area in healthy individuals was 3.9+/-0.7 cm(2), and the LMM was 99+/-27 g. In a correlation analysis, the strongest correlation of AVA was to height (r=0.75, p<0.001) and for LMM to weight (r=0.64, p<0.001). In a multiple regression analysis, the expected AVA for healthy subjects can be predicted using body height: AVA=-2.64+0.04 x(height in cm) -0.47 x w (w=0 for man, w=1 for female).In patients with aortic valve stenosis, AVA was 1.0+/-0.35 cm(2), in correlation to cath lab r=0.72, and LMM was 172+/-56 g. We compared the AS patients results with the data of the healthy subjects, where the reduction of the AVA was 28+/-10% of the expected normal value, while LMM was 42% higher in patients with AS. There was no correlation to height, weight or BSA in patients with AS. With cardiac MRI, planimetry of AVA for normal subjects and patients with AS offered a simple, fast and non-invasive method to quantify AVA. In addition LMM and EF could be determined. The strong correlation between height and AVA documented in normal subjects offered the opportunity to integrate this relation between expected valve area and definitive orifice in determining the disease of the aortic valve for the individual patient. With diagnostic MRI in patients with AS, invasive measurements of the systolic transvalvular gradient does not seem to be necessary.

Aged↗
PubMed2005

[Cervical origin of the subclavian artery: echocardiographic diagnosis in patients with monosomy 22q11].

OBJECTIVE: To assess the sensitivity and specificity of echocardiography in the detection of anomalies of the subclavian artery (cervical origin, aberrant origin from the descending aorta or isolation) in patients with monosomy 22q11. METHOD: From 1/1998 until 03/2002 we examined 57 patients with conotruncal cardiac malformations. 30 patients had pulmonary atresia and ventricular septal defect (53 %), 13 interrupted aortic arch (23 %), 9 tetralogy of Fallot (16 %) and 5 common truncus arteriosus (9 %). Echocardiographic examination included identification of the laterality of the aortic arch as well as examination of the origin of the brachiocephalic vessels. The results were compared with angiographic and intraoperative findings. Median age at echocardiographic investigation was 74 days (range 1 d - 33.4 yrs.). RESULTS: Laterality of the aortic arch was assessed correctly in all patients. 20/57 patients had a right-sided aortic arch (35 %). Echocardiography detected all anomalies of the subclavian artery (14/57 patients, 25 %, sensitivity 100 %) and excluded these anomalies correctly in 43 patients (specificity 100 %). Exact classification of the anomaly of the subclavian artery was possible in 6/6 patients with a cervical origin of the artery and in 7/8 patients with aberrant origin from the descending aorta. Monosomy 22q11 was diagnosed in 21 patients (37 %). CONCLUSION: Echocardiography achieves a high sensitivity in the detection of anomalies of the subclavian artery. The diagnosis of cervical origin of the artery, in particular, can be easily established. As this anomaly appears to be a specific marker for monosomy 22q11, echocardiography facilitates reliable identification of these patients in clinical practice.

Adolescent↗
PubMed2005

FISH studies on the telomeric regions of the T-cell acute lymphoblastic leukemia cell line CCRF-CEM.

So far, the problem of an influence of translocations on the telomeres of the involved chromosomes has not been addressed yet in human cells. Therefore, the telomeres of a karyotypically rather well characterized T-cell acute lymphoblastic leukemia (T-ALL) cell line (CCRF-CEM) with several marker chromosomes were examined using peptide nucleic acid (PNA) telomere FISH probes to compare the telomere length of these markers with that of the chromosome arms of their origin. In addition, chromosome libraries, centromeric probes, and subtelomeric DNA probes were used to further define the marker chromosomes. Two markers could be newly defined and a concise karyotype of the cell line could be obtained by these detailed examinations: 42-47,X,-X,del(5) (q35?),t(5;15)(q14;q13.2),t(8;9)(p11;p24),del(9)(:p13-->qter)/inv(9)(pter-->p12::q21-->p12::q21-->qter),+13,+20,+der(22)(p+ [HSR?])[cp]. The relative telomere length of all chromosomes showed considerable interchromosomal, intercellular, and inter-passage variation. However, it could be shown, that in four different passages of the examined cell line the observed differences between relative telomere lengths of the markers and the chromosomes of their origin, with two exceptions (short arms of del/inv9 and der22), were not significant. On the other hand, because of its mentioned variability, telomere length alone is not sufficient to reliably define the derivation of markers.

Cell Line, Tumor↗
PubMed2004

Growth of heterokaryotic monozygotic twins discordant for Ullrich-Turner syndrome during the first years of life.

The rare observation of different karyotypes in monozygotic (MZ) twins, i.e., heterokaryotic monozygosity, occurs due to chromosomal aberration in one of the twins after separation of the embryos. We report on the differences of heterokaryotic MZ Turkish twins who are discordant for Ullrich-Turner syndrome. Chromosomal analyses from peripheral lymphocytes revealed a 45,X/46,XX mosaicism in both twins. FISH analyses of buccal smears showed 99% of nuclei 45,X in twin A and 98% of nuclei 46,XX in twin B. These results are consistent with a non-mosaic 45,X and 46,XX karyotype, respectively. The girls showed a different growth pattern in the first years. As their genotype should be identical except for the number of X chromosomes, the difference in phenotype may be a pure result of loss of one X chromosome in the affected girl. Special interest is set on the spontaneous and growth hormone induced growth of the twins.

Chromosomes, Human, X↗
PubMed2004

Molecular karyotyping using an SNP array for genomewide genotyping.

BACKGROUND: Chromosomal imbalances are a major cause of developmental defects as well as cancer and often constitute the key in identification of novel disease related genes. Classical cytogenetic methods are limited in resolution and dependent on highly skilled labour, while methods with higher resolution, based on molecular cytogenetics approaches such as matrix CGH, are not widely available. METHODS: We have developed and evaluated a method we term "molecular karyotyping", using readily available and easy to handle oligonucleotide arrays originally designed for parallel genomewide analysis of over 10,000 SNPs. We show that we can easily and reliably detect unbalanced chromosomal aberrations of various sizes from as little as 250 ng of DNA on a single microarray, based on fluorescence intensity information from clusters of SNPs. RESULTS: We determined the resolution of this method through analysis of 20 trios with 21 previously confirmed subtle aberrations sizing between 0.2 and 13 Mb. Duplications and deletions of at least 5 Mb in size were reliably detectable, but detection of smaller aberrations was dependent on the number of SNPs they contained, thus seven of 10 different deletions analysed, with sizes ranging from 0.2 to 3.7 Mb, were not detectable due to insufficient SNP densitiy in the respective region. CONCLUSIONS: Deduction of reliable cut off levels for array peaks in our series of well characterised patients allows the use of the GeneChip Mapping 10K SNP array for performing rapid molecular karyotyping from small amounts of DNA for the detection of even subtle deletions and duplications with high sensitivity and specificity.

Chromosome Aberrations↗
PubMed2003

Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy.

We have recently shown that Okihiro syndrome results from mutation in the putative zinc finger transcription factor gene SALL4 on chromosome 20q13.13-13.2. There is considerable overlap of clinical features of Okihiro syndrome with other conditions, most notably Holt-Oram syndrome, a condition in part resulting from mutation of the TBX5 locus, as well as acro-renal-ocular syndrome. We analysed further families/patients with the clinical diagnosis of Holt-Oram syndrome and acro-renal-ocular syndrome for SALL4 mutations. We identified a novel SALL4 mutation in one family where the father was originally thought to have thalidomide embryopathy and had a daughter with a similar phenotype. We also found two novel mutations in two German families originally diagnosed as Holt-Oram syndrome and a further mutation in one out of two families carrying the diagnosis acro-renal-ocular syndrome. Our results show that some cases of "thalidomide embryopathy" might be the result of SALL4 mutations, resulting in an increased risk for similarly affected offspring. Furthermore we confirm the overlap of acro-renal-ocular syndrome with Okihiro syndrome at the molecular level and expand the phenotype of SALL4 mutations.

Abnormalities, Multiple↗