Hirschsprung's disease

Hirschsprung's disease (HSCR) is characterized by absence of the enteric nervous system in a variable portion of the distal gut. Affected infants usually present in the days after birth with bowel obstruction. Despite surgical advances, long-term outcomes remain variable. In the last 2 decades, great advances have been made in understanding the genes and molecular biological mechanisms that underlie the disease. In addition, our understanding of normal enteric nervous system development and how motility develops in the developing fetus and infant has also increased. This review aims to draw these strands together to explain the developmental and biological basis of HSCR, and how this knowledge may be used in the future to aid children with HSCR. © 2010.postprin

Hirschsprung disease, associated syndromes and genetics: A review

Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.published_or_final_versio

Molecular genetics of Hirschsprung's disease

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Gas chromatographic whole-cell fatty acid analysis as an aid for the identification of mixed mycobacterial cultures

Gas chromatographic analysis of whole-cell fatty acids, secondary alcohols and mycolic acid cleavage products could be a useful technique in checking mixed mycobacterial cultures. The mixed cultures were confirmed when species-specific compounds of different mycobacterial species were detected in the same chromatogram.link_to_subscribed_fulltex

Schizophrenia and hypocalcaemia: Variable phenotype of deletion at chromosome 22q11

Objective: The aim of this paper is to report the diagnosis of velo-cardio-facial syndrome (VCFS) in a patient presenting with schizophrenia and hypocalcaemia. Screening of deletion 22q11 in patients with schizophrenia is discussed. Clinical picture: We report a schizophrenic patient presenting with hypocalcaemia as the only feature of VCFS. Deletion 22q11 was confirmed by fluorescent in situ hybridisation (FISH). Treatment: The patient was treated with haloperidol 3 mg/day with resolution of psychotic symptoms. Outcome: The patient harboured some residual psychotic symptoms probably related to her irregular compliance. Conclusions: The wide range of phenotypic variability of VCFS makes screening of 22q11 deletion in schizophrenia difficult. It is proposed that screening of 22q11 deletion in schizophrenia should be selectively targeted only at patients with specific features of VCFS highly predictive of the presence of 22q11 deletion.link_to_subscribed_fulltex

Mapping of the human ribosomal large subunit protein gene RPL29 to human chromosome 3q29-qter

The human ribosomal protein L29, which we reported previously, was subsequently shown to have the same nucleotide sequence as that of cell surface heparin/heparan sulfate-binding protein, designated HP/HS interacting protein. A polymerase chain reaction-based strategy was used to distinguish the functional intron-containing gene RPL29 (HGMW-approved symbol) from multiple pseudogenes. By somatic cell hybrid analysis, radiation hybrid mapping, and fluorescence in situ hybridization, we have located RPL29 on the telomeric region of the q arm of chromosome 3. RPL29 is the most distal marker of the long arm of chromosome 3. Of the human ribosomal protein genes mapped, RPL29 is the shortest distance from another ribosomal protein gene marker, RPL35a which has also been mapped to the 3q29-qter region.link_to_subscribed_fulltex

Mycobacterial DNA not detected in liver sections from patients with primary billiary cirrhosis

Background/Aims: Recent studies in primary biliary cirrhosis have reported the detection of serum antibodies against Mycobacterium gordonae and of mycobacterial DNA in liver sections. The aim of this study was to investigate whether mycobacterial DNA is present in liver biopsy material in primary biliary cirrhosis. Methods: Archival liver biopsy specimens from 11 patients with primary biliary cirrhosis (10 female, mean age 52 years) and 11 patients with autoimmune hepatitis (10 female, mean age 53 years) were identified. Positive control tissue comprised five archival lymph node specimens from patients with tuberculous lymphadenopathy, three of which had stained positive on ZN staining, and also a fiver biopsy specimen from a patient with tuberculous hepatitis (ZN positive). Fixed sections were deparaffinised and DNA was extracted by mechanical disruption with glass beads. DNA was purified by use of diatoms and lysis in guanidinium thiocyanate in a technique previously validated for archival DNA. Primers were directed to amplify a partial 16S ribosomal RNA gene yielding the species-specific character for mycobacteria, and also to amplify the constitutively-expressed human gene GAPDH. Results: The polymerase chain reaction was shown to be capable of detecting 1 fg of M. gordonae DNA in 'spiked' samples, equivalent to 1-5 bacterial cells. No mycobacterial DNA was detected in fiver biopsy samples from either the primary biliary cirrhosis or autoimmune hepatitis groups. Of the tuberculous control sections, mycobacterial DNA was detected in four of five lymph nodes and the liver biopsy specimen. GAPDH amplification was detected in all tested samples from fiver disease and tuberculous control samples. Conclusion: These data do not support a role for mycobacteria in the aetiology of primary biliary cirrhosis.link_to_subscribed_fulltex

Association between CYP2A6 and CYP2C19 mutant alleles

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Assignment of the human 14-3-3 epsilon isoform (YWHAE) to human chromosome 17p13 by in situ hybridization

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Mapping of the human cysteine-rich intestinal protein gene CRIP1 to the human chromosomal segment 7q11.23

We report here on the mapping of a cDNA encoding for human cysteine- rich heart protein (HCRHP), a counterpart of the murine cysteine-rich intestinal protein CRIP. By somatic cell hybrid analysis and radiation hybrid mapping, we have located the gene CRIP1 (HGMW-approved symbol) on the subcentromeric region of the q arm of human chromosome 7, flanking a deletion associated with Williams syndrome.link_to_subscribed_fulltex