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PurposeTo identify the molecular basis for autosomal recessively inherited congenital non-syndromic pulverulent cataracts in a consanguineous family with four affected children.MethodsAn autozygosity mapping strategy using high density SNP microarrays and microsatellite markers was employed to detect regions of homozygosity. Subsequently good candidate genes were screened for mutations by direct sequencing.ResultsThe SNP microarray data demonstrated a 24.96 Mb region of homozygosity at 22q11.21-22q13.2 which was confirmed by microsatellite marker analysis. The candidate target region contained the beta-crystallin gene cluster and direct sequencing in affected family members revealed a novel mutation in CRYBB1 (c.2T>A; p.Met1Lys).ConclusionsTo our knowledge this is the first case of an initiation codon mutation in a human crystallin gene, and only the second report of a CRYBB1 mutation associated with autosomal recessive congenital cataracts. In addition, although a number of genetic causes of autosomal dominant pulverulent cataracts have been identified (including CRYBB1) this is the first gene to have been implicated in autosomal recessive nuclear pulverulent cataract.

Inherited immunodeficiency disorders can be caused by mutations in any one of a large number of genes involved in the function of immune cells. Here, we describe two families with an autosomal recessive inherited immunodeficiency disorder characterized by increased susceptibility to infection and autoimmunity. Genetic linkage studies mapped the disorder to chromosomal region 14q11.2, and a homozygous guanine-to-adenine substitution was identified at the last base of exon 3 immediately following the translational termination codon in the TCRα subunit constant gene (TRAC). RT-PCR analysis in the two affected individuals revealed impaired splicing of themRNA, as exon 3 was lost from the TRAC transcript. The mutant TCRα chain protein was predicted to lack part of the connecting peptide domain and all of the transmembrane and cytoplasmic domains, which have a critical role in the regulation of the assembly and/or intracellular transport of TCR complexes. We found that T cells from affected individuals were profoundly impaired for surface expression of the TCRαβ complex. We believe this to be the first report of a disease-causing human TRAC mutation. Although the absence of [TCRαβ.sup.+] T cells in the affected individuals was associated with immune dysregulation and autoimmunity, they had a surprising level of protection against infection., Introduction Inherited immunodeficiencies have provided novel insights into T and B cell development and immune function. Failure of T cell development, of whatever cause, produces the clinical syndrome of SCID, [...]

A study performs autozygosity mapping in three consanguineous families to identify the molecular basis for proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also called Fowler syndrome. Results reveal that germline mutations in FLVCR2 gene in the 14q24.3 chromosome are associated with PVHH.

Abstract Background The generation of large amounts of microarray data presents challenges for data collection, annotation, exchange and analysis. Although there are now widely accepted formats, minimum standards for data content and ontologies for microarray data, only a few groups are using them together to build and populate large-scale databases. Structured environments for data management are crucial for making full use of these data. Description The MiMiR database provides a comprehensive infrastructure for microarray data annotation, storage and exchange and is based on the MAGE format. MiMiR is MIAME-supportive, customised for use with data generated on the Affymetrix platform and includes a tool for data annotation using ontologies. Detailed information on the experiment, methods, reagents and signal intensity data can be captured in a systematic format. Reports screens permit the user to query the database, to view annotation on individual experiments and provide summary statistics. MiMiR has tools for automatic upload of the data from the microarray scanner and export to databases using MAGE-ML. Conclusion MiMiR facilitates microarray data management, annotation and exchange, in line with international guidelines. The database is valuable for underpinning research activities and promotes a systematic approach to data handling. Copies of MiMiR are freely available to academic groups under licence.

Three types of coumarin derivatives were synthetised using the Knoevenagel condensation technique. All of these compounds have been characterised by the Fourier Transform Infrared (FTIR) and the Nuclear Magnetic Resonance (NMR) spectroscopy (1H NMR, 13C NMR) to evaluate their chemical properties. The first step of synthesis involved preparing 3-acetylcoumarin 1 followed by the synthetisation of hydrazine thiosemicarbazide coumarin derivative 2 by treating thiosemicarbazide in the presence of a catalytic amount of glacial acetic acid. The hydrazinyl thiazolyl of coumarin derivative 3 was prepared using the cyclisation of compound 2 with 3-bromoacetylcoumarin. The presence of the hydrazine and thiazole groups of the latter synthetised derivatives were confirmed using an NMR analysis that depicted the bond attachment of the imine and thiazole groups in the molecular structure of the first derivative 1. An in-vitro cytotoxicity study of the synthetised coumarin derivatives were screened using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Human Periodontal Ligament Fibroblast (HPDLF) cells. The cytotoxicity study demonstrates that the coumarin derivatives which contain the hydrazinyl thiazolyl group exhibit less toxicity values at a concentration of 5.51 mM for a half maximal inhibitory concentration (IC50). The heterocyclic groups of the derivatives backbone will eventually contribute to promising biological properties of a biomaterial. [ABSTRACT FROM AUTHOR]

A correction to the article "Mutations in VIPAR Cause an Arthrogryposis, Renal Dysfunction and Cholestasis Syndrome Phenotype With Defects in Epithelial Polarization," that was published in a previous issue is presented.

Purpose: To identify the molecular basis for autosomal recessively inherited congenital non-syndromic pulverulent cataracts in a consanguineous family with four affected children., Methods: An autozygosity mapping strategy using high density SNP microarrays and microsatellite markers was employed to detect regions of homozygosity. Subsequently good candidate genes were screened for mutations by direct sequencing., Results: The SNP microarray data demonstrated a 24.96 Mb region of homozygosity at 22q11.21-22q13.2 which was confirmed by microsatellite marker analysis. The candidate target region contained the beta-crystallin gene cluster and direct sequencing in affected family members revealed a novel mutation in CRYBB1 (c.2T>A; p.Met1Lys)., Conclusions: To our knowledge this is the first case of an initiation codon mutation in a human crystallin gene, and only the second report of a CRYBB1 mutation associated with autosomal recessive congenital cataracts. In addition, although a number of genetic causes of autosomal dominant pulverulent cataracts have been identified (including CRYBB1) this is the first gene to have been implicated in autosomal recessive nuclear pulverulent cataract.