Biomedical subjects

Stefan Vermeulen

Publications and source records attributed to Stefan Vermeulen.

7 recordsLinked to original sources

PubMed2005

arrayCGHbase: an analysis platform for comparative genomic hybridization microarrays.

BACKGROUND: The availability of the human genome sequence as well as the large number of physically accessible oligonucleotides, cDNA, and BAC clones across the entire genome has triggered and accelerated the use of several platforms for analysis of DNA copy number changes, amongst others microarray comparative genomic hybridization (arrayCGH). One of the challenges inherent to this new technology is the management and analysis of large numbers of data points generated in each individual experiment. RESULTS: We have developed arrayCGHbase, a comprehensive analysis platform for arrayCGH experiments consisting of a MIAME (Minimal Information About a Microarray Experiment) supportive database using MySQL underlying a data mining web tool, to store, analyze, interpret, compare, and visualize arrayCGH results in a uniform and user-friendly format. Following its flexible design, arrayCGHbase is compatible with all existing and forthcoming arrayCGH platforms. Data can be exported in a multitude of formats, including BED files to map copy number information on the genome using the Ensembl or UCSC genome browser. CONCLUSION: ArrayCGHbase is a web based and platform independent arrayCGH data analysis tool, that allows users to access the analysis suite through the internet or a local intranet after installation on a private server. ArrayCGHbase is available at http://medgen.ugent.be/arrayCGHbase/.

Base Sequence↗

PubMed2005

An interstitial deletion of chromosome 7 at band q21: a case report and review.

We report on a girl with moderate developmental delay and mild dysmorphic features. Cytogenetic investigations revealed a de novo interstitial deletion at the proximal dark band on the long arm of chromosome 7 (7q21.1-q21.3) in all analyzed G-banded metaphases of lymphocytes and fibroblasts. Fluorescence in situ hybridization (FISH) and molecular studies defined the breakpoints at 7q21.11 and 7q21.3 on the paternal chromosome 7, with the proximal deletion breakpoint between the elastin gene (localized at 7q11.23) and D7S2517, and the distal breakpoint between D7S652 and the COL1A2 gene (localized at 7q21.3-q22.1). Deletions of interstitial segments at the proximal long arm of chromosome 7 at q21 are relatively rare. The karyotype-phenotype correlation of these patients is reviewed and discussed. The clinical findings of patients with a deletion at 7q21 significantly overlap with those of patients with maternal uniparental disomy of chromosome 7 (matUPD(7)) and Silver-Russell syndrome (SRS, OMIM 180860). Therefore, 7q21 might be considered a candidate chromosomal region for matUPD(7) and SRS.

Abnormalities, Multiple↗

PubMed2005

Molecular karyotyping: array CGH quality criteria for constitutional genetic diagnosis.

Array CGH (comparative genomic hybridization) enables the identification of chromosomal copy number changes. The availability of clone sets covering the human genome opens the possibility for the widespread use of array CGH for both research and diagnostic purposes. In this manuscript we report on the parameters that were critical for successful implementation of the technology, assess quality criteria, and discuss the potential benefits and pitfalls of the technology for improved pre- and postnatal constitutional genetic diagnosis. We propose to name the genome-wide array CGH "molecular karyotyping," in analogy with conventional karyotyping that uses staining methods to visualize chromosomes.

Cell Line↗

PubMed2004

Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations: delineation of 7q21.11 breakpoints.

Constitutional de novo complex chromosomal rearrangements (CCRs) are a rare finding in patients with mild to severe mental retardation. CCRs pose a challenge to the clinical cytogeneticist: generally CCRs are assumed to be the cause of the observed phenotypic abnormalities, but the complex nature of these chromosomal changes often hamper the accurate delineation of the chromosomal breakpoints and the identification of possible imbalances. In a first step towards a more detailed molecular cytogenetic characterization of CCRs, we studied four de novo CCRs using multicolor fluorescent in situ hybridization (M-FISH), comparative genomic hybridization (CGH), and FISH with region specific probes. These methods allowed a more refined characterization of the breakpoints in three of the four CCRs. The occurrence of 7q breakpoints in three out of these four CCRs and in 30% of reported CCRs suggested preferential involvement of this chromosomal region in the formation of CCRs. Further analysis of these 7q breakpoints revealed a 2 Mb deletion at 7q21.11 in one patient and involvement of the same region in a cryptic insertion in a second patient. This particular region contains at least 5 candidate genes for mental retardation. The other patient had a breakpoint more proximal to this region. The present data together with these from the literature provide evidence that a region within 7q21.11 may be prone to breakage and formation of CCRs.

Child, Preschool↗

PubMed2003

Ten years follow up of a boy with a complex chromosomal rearrangement: going from a > 5 to 15-breakpoint CCR.

A moderately mentally retarded 10-year-old boy of very short stature was found initially to have a complex chromosomal rearrangement (CCR) involving chromosome 1, 2, 3, 4, and 8. A balanced twelve-breakpoint CCR was suggested after extensive investigations including subtelomere FISH, whole chromosome paints, comparative genomic hybridization (CGH), multicolor FISH (MFISH), and spectral karyotyping (SKY). SKY and MFISH gave slightly discrepant results. For further clarification of the karyotype, multicolor banding (MCB) analysis and FISH with region-specific YAC probes were done. This allowed clarification of a sixteen-fragment CCR to be made, the most complex constitutional chromosomal rearrangement reported so far. Remarkably, two 'secondary' insertions originated from the interior of a 'primary' insertion by an excision/duplication event. The randomness of the fragments and the complexity of the derivative chromosomes suggest that this CCR is the result of a single meiotic event, e.g., faulty repair of a five-chromosome knot.

Child↗

PubMed2003

Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.

We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. Moreover, we suggest that the KAL1 gene product, the extracellular matrix protein anosmin-1, is involved in FGF signaling and propose that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X inactivation) explains the higher prevalence of the disease in males.

Cell Adhesion Molecules↗

PubMed2002

Kallmann syndrome in a patient with congenital spherocytosis and an interstitial 8p11.2 deletion.

We describe the hitherto smallest interstitial 8p11.2 deletion in a patient with congenital spherocytosis, dysmorphic features, and growth delay in association with hypogonadotropic hypogonadism and anosmia. The latter features are characteristic for Kallmann syndrome. In contrast to the previously reported patients with 8p deletions, the present patient showed normal intelligence. Congenital spherocytosis is one of the most common hereditary hemolytic anemias. One of the three loci for congenital spherocytosis was assigned to chromosome 8p (located between 8p11.1 and 8p21) and mutations in or loss of the ankyrin-1 gene (ANK1) were identified. Molecular analysis confirmed the de novo loss of ANK1 in our patient. Kallmann syndrome, which is characterized by hypogonadotropic hypogonadism and anosmia, can be X-linked, autosomal dominant, or autosomal recessive. So far only the X-linked KAL1 gene has been identified. The present finding suggests an autosomal locus for Kallmann syndrome at 8p11.2. The simultaneous occurrence of congenital spherocytosis, Kallmann syndrome phenotype, dysmorphic features, and growth delay in this patient points to a new contiguous gene syndrome.

Abnormalities, Multiple↗