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A Baumer

Publications and source records attributed to A Baumer.

At least 19 recordsLinked to original sources
PubMed2006

Clinical profiles of four patients with Rett syndrome carrying a novel exon 1 mutation or genomic rearrangement in the MECP2 gene.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG binding protein 2 (MeCP2). Recently, a new isoform of MeCP2 including exon 1 was identified. This new isoform is more abundantly expressed in brain than the isoform including exons 2-4. Very little is known about the phenotypes associated with mutations in exon 1 of MECP2 since only a limited number of RTT patients carrying such mutations have been identified so far. In this study, we screened a cohort of 20 girls with RTT for exon 1 mutations by sequencing and multiplex ligation-dependent probe amplification (MLPA). We identified one girl with a novel exon 1 mutation (c.30delCinsGA) by sequencing and three with genomic rearrangements by MLPA. Comparison of the phenotypes showed that the girls carrying a mutation or rearrangement encompassing exon 1 were more severely affected than the girls with rearrangements not affecting exon 1.

Adolescent↗
PubMed2006

Jacobsen syndrome and Beckwith-Wiedemann syndrome caused by a parental pericentric inversion inv(11)(p15q24).

Here we report on a male infant presenting the typical pattern of Jacobsen syndrome including trigonocephaly, thrombocytopenia, congenital heart defect, urethral stenosis, and partial agenesis of the corpus callosum. Conventional karyotyping, FISH, SKY and CGH analyses showed that the region distal to the MLL locus on 11q23 was lost and replaced by the distal region of 11p, leading to a partial trisomy of 11p and a partial monosomy of 11q. According to ISCN (1995) the karyotype can be described as 46,XY,add(11)(q2?3). ish 11ptel(D11S2071x3),11qtel(VIJyRM2072x1). Array-CGH analysis allowed us to narrow down the breakpoints to 11p15.1 and 11q24.1. Methylation analyses of genes located on 11p showed an increased level of the non-methylated paternal allele of the KCNQ1OT1 gene, confirming the concomitant presence of Beckwith-Wiedemann syndrome (BWS). The phenotype resulting from the 11q deletion seems to dominate the phenotype due to the distal 11p trisomy. Investigation of the parents revealed that this chromosomal rearrangement was caused by a paternal pericentric inversion inv(11)(p15q24). Since chromosomal aberrations like the one described here can easily be overlooked during routine chromosome analysis, combined FISH analysis using subtelomeric and possibly additional probes should be applied if there is any doubt about the integrity of telomeric regions.

Abnormalities, Multiple↗
PubMed2005

Unbalanced 18q/21q translocation in a patient previously reported as monosomy 21.

We describe a patient in whom full monosomy 21 was initially assumed from routine GTG-banded karyotyping. Re-examination with chromosome painting demonstrated an unbalanced translocation between the long arms of chromosomes 18 and 21. Fluorescence in situ hybridisation (FISH) and microsatellite marker analysis revealed partial monosomy of chromosome 21 (pter-q21) and 18(q22-qter). The patient, 18 years old at the second examination, revealed multiple dysmorphic features, genital hypoplasia, dilated cerebral ventricles, muscular hypotonia and severe mental retardation. In not one out of all patients investigated postnatally in whom an initial examination had revealed monosomy 21, this could be confirmed by FISH; in all of them, re-examination detected an unbalanced rearrangement leading to only partial monosomy 21 plus partial monosomy of another chromosome to which the distal 21q segment was attached. Thus, it is still highly likely that full monosomy 21 is incompatible with intra-uterine survival.

Abnormalities, Multiple↗
PubMed2005

A case with de novo interstitial deletion of chromosome 7q21.1-q22.

A case with de novo interstitial deletion of chromosome 7q21.1-q22: A patient with multiple congenital anomalies was found to have a de novo proximal interstitial deletion of chromosome 7q21.1-q22. The patient was 10.5 years of age, and manifestations include growth retardation (below 3rd percentile), mental retardation, mild microcephaly, hypersensitivity to noise, mild spasticity, short palpebral fissures, alternant exotropia, compensated hypermetropic astigmatism, hypotelorism, hypoplastic labia majora and minora, clinodactyly of fingers 4 and 5. Molecular studies revealed that the deletion had a paternal origin, while chromosomes of both parents cytogenetically were shown to be normal. Molecular, and fluorescence in situ hybridization (FISH) analyses confirmed no deletion at the Williams-Beuren Syndrome region. Some of the heterogeneous clinical findings were consistent with previously reported cases of same chromosomal breakpoints.

Abnormalities, Multiple↗
PubMed2005

M-FISH applications in clinical genetics.

Until recently, presence of de novo marker or derivative chromosomes was quite problematic for genetic counseling especially in prenatal diagnosis, because characterization of marker and derivative chromosomes by conventional cytogenetic techniques was nearly impossible. However, recently developed molecular cytogenetic technique named Multicolor Fluorescence in Situ Hybridization (M-FISH) which paints all human chromosomes in 24 different colors allows us to characterize marker and derivative chromosomes in a single hybridization. In this study, we applied M-FISH to determine the origin of 3 marker and 3 derivative chromosomes. Marker chromosomes were found to originate from chromosome 15 in two postnatal and one prenatal case. Of these, one of the postnatal cases displayed clinical findings of inv dup (115) syndrome and the other of infertility, and the prenatal case went through amniocentesis due to the triple test results. Karyotypes of the patients with derivative chromosomes were designated as 46,XY,der (21)t(1;21)(q32;p11), 46,XX,der(8)t(8;9)(p23;p22) and 46,XX,der(18)t(18;20)(q32;p11.2) according to cytogenetic and M-FISH studies. All of the M-FISH results were confirmed with locus specific or whole chromosome painting probes. The case with der (8)t(8;9) had trisomy 9(p22-pter) and monosomy 8(p23-pter) due to this derivative chromosome. The case with der(18)t(18;20) had trisomy 20(p11.2-pter) and monosomy 18(q32-qter). Parental origins of the derivative chromosomes were analyzed using microsatellite markers located in the trisomic chromosomal segments. Patients' clinical findings were compared with the literature.

Adult↗
PubMed2004

Strong temperature dependence of irradiation effects in organic layers.

Radiation damage of self-assembled monolayers, which are prototypes of thin organic layers and highly organized biological systems, shows a strong dependence on temperature. Two limiting cases could be identified. Reactions involving transport of single atoms and small fragments proceed nearly independent of temperature. Reactions requiring transport of heavy fragments are, however, efficiently quenched by cooling. We foresee the combined use of temperature and irradiation by electrons or photons for advanced tailoring of self-assembled monolayers on surfaces. In addition, our results have direct implications for cryogenic approaches in advanced electron and x-ray microscopy and spectroscopy of biological macromolecules and cells.

Biomimetic Materials↗
PubMed2004

Non-random asynchronous replication at 22q11.2 favours unequal meiotic crossovers leading to the human 22q11.2 deletion.

BACKGROUND: Analyses of the replication timing at 22q11.2 were prompted by our finding of a statistically significant bias in the origin of the regions flanking the deletion site in patients with 22q11.2 deletions, the proximal region being in the majority of cases of grandmaternal origin. We hypothesised that asynchronous replication may be involved in the formation of the 22q11.2 deletion, the most frequently occurring interstitial deletion in humans, by favouring the mispairing of low-copy repeats. METHODS: Replication timing during S phase at 22q11.2 was investigated by fluorescent in situ hybridisation on interphase nuclei. We report on the detection of non-random asynchronous replication at the human chromosome region 22q11.2, an autosomal locus believed not to contain imprinted genes. RESULTS: Asynchronous replication at 22q11.2 was observed without exception in all 20 tested individuals; these comprised individuals with structurally normal chromosomes 22 (10 cases), individuals with translocations involving the locus 22q11.2 (eight cases), and patients with a 22q11.2 deletion (two cases). The non-random nature of the asynchronous replication was observed in all individuals for whom the chromosomes 22 were distinguishable. The earlier replicating allele was found to be of paternal origin in all cases where the parental origin of the translocation or deletion was known.

Chromosome Deletion↗
PubMed2003

Parental origin of the two additional haploid sets of chromosomes in an embryo with tetraploidy.

We report on the molecular investigations performed on an embryo with tetraploidy, karyotype 92,XXXY. The embryo was spontaneously aborted after eight weeks of gestation. Molecular analyses were performed in order to determine the parental origin and mode of formation of the two additional haploid sets of chromosomes. Microsatellite markers mapping to pericentromeric chromosome regions were used. Our results show a maternal origin of one additional set of chromosomes most likely due to the incorporation of the polar body of meiosis I and a paternal origin of the second additional set of chromosomes most likely due to dispermy. The karyotype 92,XXXY is rather unusual, indeed the vast majority of cases with tetraploidy have the karyotypes 92,XXXX or 92,XXYY. To the best of our knowledge this is the first case with 92,XXXY for which molecular investigations have been performed.

Abortion, Spontaneous↗
PubMed2002

Meiotic origin of two ring chromosomes 18 in a girl with developmental delay.

We report on the cytogenetic, fluorescence in situ hybridization (FISH), and molecular results obtained for a patient with a mild and nonspecific pattern of minor anomalies and developmental delay. In the proband's karyotype one chromosome 18 was replaced by a ring chromosome 18 in all metaphases, with deletion of the terminal regions. Furthermore, 56% of the metaphases contained a supernumerary small ring chromosome. Microdissection followed by FISH analysis demonstrated that the small ring chromosome consisted of material from the pericentromeric region of chromosome 18. The karyotype was defined as 46,XX,r(18)(p11.3q23)[88]/47,XX,r(18)(p11.3q23)+r(18)(p11.22q12.2)[112]. Thus, the patient has a deletion at 18pter and at 18qter, and a mosaic partial trisomy of the pericentromeric region of chromosome 18. We undertook molecular analysis using DNA samples of the patient and her parents in order to clarify the origin and possible mode of formation of the chromosome abnormalities. Our results show a paternal origin of the structurally normal chromosome 18 and a maternal origin for both ring chromosomes 18. Interestingly, the smaller ring chromosome did not arise postzygotically from the larger ring, since the two ring chromosomes contain genetic material derived from the two different maternal chromosomes 18. The abnormalities appear to have arisen during a meiotic division, and it could be speculated that both ring chromosomes 18 arose simultaneously due to complex pairing and recombination events. After fertilization, the small ring chromosome was lost in a subset of cells, thus leading to mosaicism.

Child↗
PubMed2001

A novel MSP/DHPLC method for the investigation of the methylation status of imprinted genes enables the molecular detection of low cell mosaicisms.

We describe a new procedure for the analysis of the methlyation status of imprinted genes based on methylation-specific PCR followed by denaturing high performance liquid chromatography (MSP/DHPLC). The method offers a rapid and very reliable alternative to conventional methods used for such purposes such as Southern blots and methylation specific PCR (allele-specific MSP). The efficient resolution of the differentially methylated alleles is demonstrated for two human imprinted genes, namely the SNRPN gene and the LIT1 gene (KCNQ1OT1). Abnormal imprinting of the two genes is associated with the Angelman/Prader-Willi syndromes and the Beckwith-Wiedemann syndrome, respectively. The MSP/DHPLC method is based on PCR amplification of gene segments which show parent-of-origin specific methylation. Genomic DNA is subjected to an in vitro bisulfite treatment prior to PCR amplifications using primers specific for modified DNA. Both alleles are theoretically amplified with equal efficiency and are represented by identically sized PCR products; they differ, however, at a number of positions within the amplified DNA segment. The DHPLC analysis allows a very efficient resolution of the two populations of PCR products. The high sensitivity and quantitative properties of the MSP/DHPLC method are illustrated based on its ability to reveal a low cell mosaicism in an infant with a maternal uniparental disomy 15 (i.e., Prader-Willi syndrome patient). The minor cell line (approximately 8% in blood) was not detectable with conventional molecular analysis. While the detection of low cell mosaicisms of structurally abnormal chromosomes usually relies on cytogenetic studies, the MSP/DHPLC method described here not only offers an alternative at the molecular level, but may also reveal mosaicisms concerning structurally intact chromosomes.

Adult↗
PubMed2001

Velofacial hypoplasia (Sedlackova syndrome): a variant of velocardiofacial (Shprintzen) syndrome and part of the phenotypical spectrum of del 22q11.2.

UNLABELLED: In 1955, a pattern of velar hypoplasia causing hypernasal speech and associated facial dysmorphism was observed in 26 children of Czech origin. Further cases with submucous cleft and/or cardiac anomalies were described. In 1978 velocardiofacial syndrome (VCFS) was reported, a condition very similar to velofacial hypoplasia (Sedlackova syndrome) apart from overt clefts instead of velar hypoplasia. In 1990 it was suggested that both syndromes might be variants of the same clinical entity. To test this hypothesis we performed fluorescence in situ hybridisation using the DiGeorge/VCFS region specific probe D22S75 on 20 patients originally classified as Sedlackova syndrome as well as molecular investigations for a subset of these patients. A 22q11.2 deletion was found in 16/20 patients. Thus, our results confirm the aforementioned hypothesis and expand the long list of clinical diagnoses associated with del 22q11.2. CONCLUSION: Velofacial hypoplasia (Sedlackova syndrome) and velocardiofacial (Shprintzen) syndrome have a corresponding phenotype and are both associated with del 22q11.2.

Abnormalities, Multiple↗
PubMed2001

Submicroscopic terminal deletions and duplications in retarded patients with unclassified malformation syndromes.

Unbalanced submicroscopic subtelomeric chromosomal rearrangements represent a significant cause of unexplained moderate to severe mental retardation with and without phenotypic abnormalities. We investigated 254 patients (102 from Zürich, 152 from Liège) for unbalanced subtelomeric rearrangements by using fluorescence in situ hybridisation with probes mapping to 41 subtelomeric regions. Mental retardation combined with a pattern of dysmorphic features, with or without major malformations, and growth retardation and a normal karyotype by conventional G-banding were the criteria of inclusion. Selection criteria were more restrictive for the Zürich series in terms of clinical and cytogenetic pre-investigation. We found 13 unbalanced rearrangements and two further aberrations, which, following the investigation of other family members, had to be considered as variants without influence on the phenotype. The significant aberrations included three de novo deletions (two of 1pter, one of 5pter), three de novo duplications (8pter, 9pter, Xpter), one de novo deletion 13qter-duplication 4qter, and five familial submicroscopic translocations [(1q;18p), (2q;4p), (2p;7q), (3p;22q), (4q;10q), (12p;22q)], most of them with several unbalanced offspring with deletion-duplication. Although the incidence of abnormal results was higher (10/152) in the Liège versus the Zürich series (3/102), similar selection criteria in Zürich as in Liège would have resulted in an incidence of 7/106 and thus similar figures. In our series, submicroscopic unbalanced rearrangements explain the phenotype in 13/254 study probands. The most important selection criterion seems to be the presence of more than one affected member in a family. An examination of subtelomeric segments should be included in the diagnostic work-up of patients with unexplained mental retardation combined with physical abnormalities, when a careful conventional examination of banded chromosomes has yielded a normal result and a thorough clinical examination does not lead to another classification. The proportion of abnormal findings depends strongly on selection criteria: more stringent selection can eliminate some examinations but necessitates a high workload for experienced clinical geneticists. Once the costs and workload of screening are reduced, less selective approaches might finally be more cost-effective.

Adult↗
PubMed2001

De novo unbalanced t(11q;21q) leading to a partial monosomy 21pter-q22.2 and 11q24-qter in a patient initially diagnosed as monosomy 21.

We describe a patient in whom full monosomy 21 was initially assumed from routine GTG banded karyotyping. Re-examination with chromosome painting demonstrated an unbalanced translocation between the long arms of chromosomes 11 and 21. Fluorescence in situ hybridization (FISH) and microsatellite marker analysis revealed partial monosomy of chromosome 21 (pter-q22.2) and 11 (q24-qter). The patient was prematurely born in the 31st week of gestation and expired 3 days after delivery. She showed multiple minor anomalies, a complex cardio-vascular malformation, intestinal malrotation and cerebellar hypoplasia.

Abnormalities, Multiple↗
PubMed2000

A novel locus (DFNA24) for prelingual nonprogressive autosomal dominant nonsyndromic hearing loss maps to 4q35-qter in a large Swiss German kindred.

Nonsyndromic hearing loss is one of the most genetically heterogeneous traits known. A total of 30 autosomal dominant nonsyndromic hearing-loss loci have been mapped, and 11 genes have been isolated. In the majority of cases, autosomal dominant nonsyndromic hearing loss is postlingual and progressive, with the exception of hearing impairment in families in which the impairment is linked to DFNA3, DFNA8/12, and DFNA24, the novel locus described in this report. DFNA24 was identified in a large Swiss German kindred with a history of autosomal dominant hearing loss that dates back to the middle of the 19th century. The hearing-impaired individuals in this kindred have prelingual, nonprogressive, bilateral sensorineural hearing loss affecting mainly mid and high frequencies. The DFNA24 locus maps to 4q35-qter. A maximum multipoint LOD score of 11.6 was obtained at 208.1 cM at marker D4S1652. The 3.0-unit support interval for the map position of this locus ranges from 205.8 cM to 211.7 cM (5.9 cM).

Child, Preschool↗
PubMed2000

Prenatal diagnosis of mosaicism for a del(22)(q13).

A case of prenatally detected mosaicism for a del(22)(q13) is reported. CVS was performed because of abnormal fetal ultrasound findings: cystic 'tumour' in the fetal neck and the upper thoracic aperture. Karyotypes from chorionic villi were suspicious of an aberration concerning the long arm of one chromosome 22. FISH analysis demonstrated mosaicism for a distal 22q deletion in fetal fibroblasts. The deletion was postnatally confirmed by FISH with a chromosome-specific 22q probe. The 'tumour' on autopsy turned out to be cystic thymic tissue. Apart from this, no other obvious fetal anomalies were found.

Adult↗
PubMed2000

Isolated central form of tetrahydrobiopterin deficiency associated with hemizygosity on chromosome 11q and a mutant allele of PTPS.

6-Pyruvoyl-tetrahydropterin synthase (PTS or PTPS) is involved in tetrahydrobiopterin (BH(4)) biosynthesis, the cofactor for various enzymes including the aromatic amino acid hydroxylases. Inherited PTPS deficiency is a heterogeneous disease with different phenotypes leading to BH(4) depletion. The severe form of PTPS deficiency causes hyperphenylalaninemia and monoamine neurotransmitter deficiency, whereas the mild form gives rise to hyperphenylalaninemia only. From 228 patients with PTPS deficiency at least 32 different mutant alleles have been identified on its corresponding gene, located on chromosome 11q22.3-q23.3. Here we describe a new allele from a child with PTPS deficiency who exhibited a mild but transient form of hyperphenylalaninemia, yet was deficient in CSF monoamines. The patient was found to carry, on her genomic DNA and cDNA, a homozygous A>G transition, leading to PTPS codon alteration Tyr99 to Cys (Y99C). The mother and several members of the maternal family were carriers of the Y99C allele, also verified by the reduced PTPS enzyme activity in erythrocytes. By cytogenetic, molecular, and FISH analyses, a de novo deletion spanning from 11q14 to 11q23.3 on the patient's paternal chromosome was mapped, establishing hemizygosity of the Y99C allele. The PTPS mutation observed in this patient generates a novel phenotype with an apparently isolated central form of BH(4) deficiency.

Alleles↗
PubMed2000

Maternal uniparental disomy 7--review and further delineation of the phenotype.

UNLABELLED: Uniparental disomy (UPD) is defined as the inheritance of both homologous chromosomes from only one parent. So far, maternal UPD 7 has been described in 28 cases. Here, we report 4 new cases, present clinical information of 5 cases previously reported by us, and review the clinical and molecular findings of all 32 cases. We found a phenotype characterized by pre- and postnatal growth retardation, occipitofrontal head circumference in the lower normal range, a triangular face, and retarded bone maturation. Findings of the facial gestalt included a high and broad forehead and a pointed chin. A broad mouth with down-turned corners, prominent ears, café-au-lait spots, hemihypotrophy, or clinodactyly were rarely present. Psychomotor development was delayed in 6 cases. The clinical findings strikingly resemble the phenotype of the heterogeneous Silver-Russell syndrome (SRS). Other anomalies were less frequently found than in SRS. Molecular investigations revealed 11 cases with isodisomy and 17 cases with heterodisomy. In 4 cases this information was not available. From the allelic distribution of the microsatellites investigated, 9 cases might be the consequence of an error at maternal meiosis I, and 6 cases might be due to non-disjunction at maternal meiosis II. Three of the 17 heterodisomic cases had trisomy 7 in chorionic villi, in the remaining cases no prenatal diagnosis through chorionic villus sampling was reported. CONCLUSION: Maternal UPD 7 should investigated in children with pre- and postnatal growth retardation anda facial gestalt characterized by a high and broad forehead and a pointed chin, as well as in cofined placental mosaicism for trisomy 7.

Abnormalities, Multiple↗