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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously developed a method of partitioning genetic variance of a quantitative trait to loci in specific chromosomal regions. In this paper, we compare this method--multipoint IBD (identical by descent) method (MIM)--with parametric multipoint linkage analysis (MLINK). A simulation study was performed comparing the methods for the major-locus, mixed, and two-locus models. The criterion for comparisons between MIM and MLINK was the average lod score from multiple replicates of simulated data sets. The effect of gene frequency, dominance, model misspecification, marker spacing, and informativeness are also considered in a smaller set of simulations. Within the context of the models examined, the MIM approach was found to be comparable in power with parametric multipoint linkage analysis when (a) parental data are unknown, (b) the effect of the major locus is small and there is additional genetic variation, or (c) the parameters of the major-locus model are misspecified. The performance of the MIM method relative to MLINK was markedly lower when the allele frequency at the trait locus was .2 versus .5, particularly for the case when parental data were assumed to be known. Dominance at the trait major locus, as well as marker spacing and heterozygosity, did not appear to have a large effect on the ELOD comparisons.
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PMID:Comparison of a multipoint identity-by-descent method with parametric multipoint linkage analysis for mapping quantitative traits. 153 96

Ichthyosis bullosa of Siemens (IBS; MIM: 146800) is an autosomal dominant disorder of keratinization characterized by epidermolytic hyperkeratosis without erythroderma. The clinical features are less marked than those of bullous congenital ichthyosiform erythroderma with relatively mild hyperkeratosis usually limited to the skin flexures. Mutations in the epithelial cytokeratin 2e (K2e), which is expressed in a differentiation-specific fashion in the upper spinous and granular layers of the epidermis, have been shown to cause IBS. We detected a novel mutation in a three generation kindred with IBS (1448T-->A) within exon 7 of the KRT2E gene. This is predictive of an I483N substitution in the 2B domain of K2e. This extends the range of mutations reported to date and illustrates the usefulness of molecular genetics in the diagnosis of this disorder.
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PMID:A novel mutation in the 2B domain of keratin 2e causing ichthyosis bullosa of Siemens. 1116 82

Ichthyosis bullosa of Siemens (IBS, MIM 146800) is a unique congenital ichthyosis characterized by mild epidermal hyperkeratosis over flexural areas, blister formation and the development of superficially denuded areas of hyperkeratotic skin. It is clinically difficult to distinguish severe IBS from mild bullous congenital ichthyosiform erythroderma (BCIE, MIM 113800). In the current literature, 19 IBS families with keratin 2e (K2e) mutations have been reported, despite only five IBS families having been reported before the first identification of K2e mutation in 1994. We studied four patients from three Japanese IBS families. They had previously been misdiagnosed as having BCIE before the correct diagnosis was made after mutation detection. To detect the pathogenic mutations, we performed direct sequencing of the entire coding regions of KRT2E encoding K2e in the patients and healthy family members. K2e mutations, a 1469T-->C transition (L490P) and a 1477G-->A transition (E493K) within the conserved 2B helix termination motif of the rod domain were detected in the families and the definite diagnosis of IBS was made in the four cases. The present results indicate that IBS is not such a rare entity as was previously thought, and accurate diagnosis is now available by mutation analysis.
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PMID:Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular genetic testing. 1594 9