The application of CT for 3D visualization of concealed bodies.

In forensic radiology, computed tomography (CT) is often used as a medical imaging technique to identify the cause and manner of death of deceased victims of a possible crime. In this study, medical imaging is used to examine concealed bodies and packaging materials. Medical imaging techniques, mainly CT scan, were used to scan packaged or concealed bodies inside containers to identify clues and evidence indicating whether a crime might have been committed.

Design of the FemCure study: prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care.

Background: In women, anorectal infections with Chlamydia trachomatis (CT) are about as common as genital CT, yet the anorectal site remains largely untested in routine care. Anorectal CT frequently co-occurs with genital CT and may thus often be treated co-incidentally. Nevertheless, post-treatment detection of CT at both anatomic sites has been demonstrated.

A stochastic model of the processes in PCR based amplification of STR DNA in forensic applications.

In forensic DNA profiling use is made of the well-known technique of PCR. When the amount of DNA is high, generally unambiguous profiles can be obtained, but for low copy number DNA stochastic effects can play a major role. In order to shed light on these stochastic effects, we present a simple model for the amplification process.

The unfolding clinical spectrum of holoprosencephaly due to mutations in SHH, ZIC2, SIX3 and TGIF genes.

Holoprosencephaly is a severe malformation of the brain characterized by abnormal formation and separation of the developing central nervous system. The prevalence is 1:250 during early embryogenesis, the live-born prevalence is 1:16 000. The etiology of HPE is extremely heterogeneous and can be teratogenic or genetic.

Identical cryptic partial monosomy 20pter and trisomy 20qter in three adult siblings due to a large maternal pericentric inversion: detection by MLPA and breakpoint mapping by SNP array analysis.

Genotypic and phenotypic data are presented on three adult siblings with mild to moderate mental retardation and mild dysmorphic features. All three siblings showed a chromosome 20 gain at the q-telomere and loss at the p-telomere in routine subtelomeric MLPA screening. Analysis of GTG-banded chromosomes did not detect any abnormalities, but subtelomeric fluorescent in situ hybridization (FISH) confirmed cryptic partial monosomy of chromosome region 20p13 --> 20pter and cryptic partial trisomy of chromosome region 20q13.

Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function.

Background: Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain. There are several important HPE mutational target genes, including the transcription factor SIX3, which encodes an early regulator of Shh, Wnt, Bmp and Nodal signalling expressed in the developing forebrain and eyes of all vertebrates.

Objective: To characterise genetic and clinical findings in patients with SIX3 mutations.

The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism.

Mutations of the ZIC2 transcription factor gene are among the most common heterozygous variations detected in holoprosencephaly (HPE) patients, a patient group who lack critical midline forebrain specification due to defective embryonic signaling during development. Recent studies indicate that complete deficiency of the related murine Zic2 transcription factor can also be a contributing factor to variable midline deficiencies, presenting during mid-gastrulation, that could explain similar forebrain anomalies in this model system. Here we collect and summarize all available mutations in the human ZIC2 gene detected in HPE patients (21 published and 62 novel).

Contiguous gene syndrome due to a maternally inherited 8.41 Mb distal deletion of chromosome band Xp22.3 in a boy with short stature, ichthyosis, epilepsy, mental retardation, cerebral cortical heterotopias and Dandy-Walker malformation.

Microdeletions of Xp22.3 are associated with contiguous gene syndromes, the extent and nature of which depend on the genes encompassed by the deletion. Common symptoms include ichthyosis, mental retardation and hypogonadism.

Validation of preimplantation genetic diagnosis by PCR analysis: genotype comparison of the blastomere and corresponding embryo, implications for clinical practice.

The aim of this study was to validate the overall preimplantation genetic diagnosis (PGD)-PCR procedure and to determine the diagnostic value. Genotyped embryos not selected for embryo transfer (ET) and unsuitable for cryopreservation after PGD were used for confirmatory analysis. The PGD genotyped blastomeres and corresponding embryos were compared, and morphology was scored on Day 4 post fertilization.

Holoprosencephaly and preaxial polydactyly associated with a 1.24 Mb duplication encompassing FBXW11 at 5q35.1.

Holoprosencephaly (HPE) is the most common developmental defect affecting the forebrain and midface in humans. The aetiology of HPE is highly heterogeneous and includes both environmental and genetic factors. Here we report on a boy with mild mental retardation, lobar HPE, epilepsy, mild pyramidal syndrome of the legs, ventricular septal defect, vesicoureteral reflux, preaxial polydactyly, and facial dysmorphisms.

[From gene to disease; the PABN1 gene and oculopharyngeal muscular dystrophy].

Oculopharyngeal muscular dystrophy is a rare disease, presenting with bilateral ptosis and dysphagia, followed by slow progressive muscle weakness. The pathological hallmark of the disease is the presence of intranuclear inclusions in muscle cells. Inheritance is autosomal dominant in almost all cases.

Rett syndrome in females with CTS hot spot deletions: a disorder profile.

From a series of 107 females with Rett syndrome (RTT), we describe the long-term history of ten females with a deletion in the C-terminus of the MECP2 gene. We observed that their disorder profile is clinically recognizable with time and different from other atypical and milder RTT phenotypes. In females with hot spot deletions in the C-terminus, dystonia is present from childhood and results in a serious spine deformation in spite of preventive measures.

Mosaic trisomy 11p in monozygotic twins with discordant clinical phenotypes.

We report on monozygotic (MZ) twins with a de novo mos 46,XX,der(15)t(11;15)(p12;p11.2)/46,XX karyotype varying in different tissues. The clinical presentation and findings at the cytogenetic level are described.

Preimplantation genetic diagnosis of spinocerebellar ataxia 3 by (CAG)(n) repeat detection.

Spinocerebellar ataxia 3 (SCA3) is an autosomal dominant neurodegenerative disorder characterized by variable expression and a variable age of onset. SCA3/MJD (Machado-Joseph disease) is caused by an expansion of a (CAG)(n) repeat in the MJD1 gene on chromosome 14q32.1.

Rett syndrome in adolescent and adult females: clinical and molecular genetic findings.

Rett syndrome (RTT) is a neurodevelopmental disorder which is diagnosed clinically. We report on 30 adolescent and adult females with classical or atypical RTT of whom 24 have a MECP2 mutation. In these 24 females, the clinical manifestations, degree of severity, and disorder profiles are discussed as well as the genotype phenotype correlation.

Neurodevelopmental disorders in males related to the gene causing Rett syndrome in females (MECP2).

Mutations in the MECP2 (methyl-CpG-binding protein 2) gene are known to cause Rett syndrome, a well-known and clinically defined neurodevelopmental disorder. Rett syndrome occurs almost exclusively in females and for a long time was thought to be an X-linked dominant condition lethal in hemizygous males. Since the discovery of the MECP2 gene as the cause of Rett syndrome in 1999, MECP2 mutations have, however, also been reported in males.

[From gene to disease; craniosynostosis syndromes due to FGFR2-mutation].

One of the genes involved in craniosynostosis syndromes is the fibroblast growth factor receptor 2 (FGFR2) gene, a tyrosine kinase receptor gene. Upon ligand binding the FGFR2 receptors dimerise, and this is followed by activation of the intracellular tyrosine kinase domains. This initiates a cascade of signals that influence cell division and differentiation.

Mosaic telomeric (2;14) association in a child with motor delay.

In a 6-year-old girl referred because of mild motor delay and hyperextensible joints, chromosome analysis disclosed a derivative chromosome consisting of end-to-end fusion of chromosomes 2 and 14. Two cell lines existed in which this telomere association was present, one with a 45,XX,tas(2;14)(q37;p11) karyotype and one with a 45,XX,tas(2;14) (q37;q32) karyotype. The cell line with the telomeric fusion of 2q and 14p was present in 90% of the cells; a telomeric fusion of 2q and 14q was seen in the remaining 10% of the cells.

Multiplex PCR of polymorphic markers flanking the CFTR gene; a general approach for preimplantation genetic diagnosis of cystic fibrosis.

Cystic fibrosis (CF) is the first monogenic disorder for which single cell preimplantation genetic diagnosis (PGD) has been successfully applied. The spectrum of mutations in CF is extremely heterogeneous, and hence, the development of mutation-specific PGD protocols is impracticable. The current study reports the development and evaluation of a general multiplex marker polymerase chain reaction (PCR) protocol for PGD of CF.

Multicolour fluorescent detection and mapping of AFLP markers in chicken (Gallus domesticus).

We describe the mapping of amplified restriction fragment polymorphism (AFLP) markers in chicken (Gallus domesticus) using a multi-colour fluorescent detection system. DNA was used from a population consisting of four families with a total of 183 F2 individuals. The enzyme combination EcoRI/TaqI was used for double digestion, and fluorescently labelled fragments were analysed on an ABI PRISM 377 DNA sequencer.

Nucleotide sequence of the chicken HMGI-C cDNA and expression of the HMGI-C and IGF1 genes in autosomal dwarf chicken embryos.

Mutations in the genes for high mobility group protein I-C (HMGI-C) and insulin-like growth factor 1 (IGF1) are known to be responsible for dwarf phenotypes in the mouse. Because the locus for autosomal dwarfism (adw) in the chicken maps to a region which is syntenic to a region in the human and mouse in which the HMGI-C and IGF1 genes are located, HMGI-C and IGF1 are likely candidate genes for adw in the chicken. In this study their possible role in the establishment of this phenotype has been investigated.

The HMGI-C gene is a likely candidate for the autosomal dwarf locus in the chicken.

In order to map the autosomal dwarf (adw) locus in the chicken, 11 segregating families were created. Initially five of these families were used for a linkage experiment in which the genome was scanned with microsatellites using a technique called bulked segregant analysis. Subsequently animals from 11 families were typed individually for microsatellites that appeared to be linked.

In situ hybridization and flow cytometric analysis of colorectal tumours suggests two routes of tumourigenesis characterized by gain of chromosome 7 or loss of chromosomes 17 and 18.

Chromosomal aberrations in colonic tumourigenesis were investigated by fluorescence in situ hybridization (FISH) with centromere-specific DNA probes and correlated to flow cytometry (FCM) results in a series of tissues including normal colonic epithelium, adenomas, and carcinomas, as well as adenomas adjacent to carcinomas. No numerical chromosome aberrations were detected in normal colonic epithelium, except for an extra chromosome X in one case. In the adenomas, the most frequently occurring chromosome aberration was a trisomy for chromosome 7, occurring in 37 per cent of the cases.