Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The three genes (LAMA3, LAB3 and LAMC2) that encode the anchoring filament protein, laminin 5, may all harbour pathogenetic mutations in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa (JEB). Recently, one particular mutation, R635X in the LAMB3 gene, has been found to account for approximately 40% of all JEB laminin 5 mutations (Kivirikko et al., Hum Mol Genet 1996; 5: 231-7). In this study, we assessed the frequency of this mutation in 12 British patients with lethal (Herlitz) JEB using PCR amplification of genomic DNA and restriction endonuclease digestion. The mutation R635X was fond in seven of 24 (29%) mutant alleles, confirming its relative frequency within the British gene pool. In addition, haplotype analysis using intragenic polymorphisms showed that the mutation arose on at least four different haplotype backgrounds, suggesting it represents a mutational hotspot rather than propagation of a common British ancestral allele. These findings support the hypermutable nature of this CpG dinucleotide and have implications in screening for laminin 5 gene mutations in British and other patients with JEB.
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PMID:A recurrent laminin 5 mutation in British patients with lethal (Herlitz) junctional epidermolysis bullosa: evidence for a mutational hotspot rather than propagation of an ancestral allele. 920 97

Herlitz junctional epidermolysis bullosa is a heritable bullous disease caused by mutations found primarily in the b3 chain of laminin 5 (LAMB3). In this study, we examined the LAMB3 gene for mutations in 22 Herlitz junctional epidermolysis bullosa families, and identified 15 distinct mutations, eight of them previously unreported, bringing the total number of distinct Herlitz junctional epidermolysis bullosa mutations in LAMB3 to 35. Examination of the mutation database revealed several recurrent mutations that have been reported, as well as six previously unreported. All recurrent mutations may be readily detected by polymerase chain reaction of genomic DNA and restriction endonuclease digestion. Mutation screening and prenatal diagnosis of families at risk may be expedited by molecular testing for these recurrent mutations prior to screening the entire gene. Finally, the U.S. population carrier risk for Herlitz junctional epidermolysis bullosa and all variants of junctional epidermolysis bullosa was calculated to be one in 781 and one in 350, respectively, while the overall epidermolysis bullosa carrier frequency was calculated to be one in 113. These data allow accurate testing, counseling, and risk calculation for nuclear families, as well as extended family members at risk for junctional epidermolysis bullosa.
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PMID:Herlitz junctional epidermolysis bullosa: novel and recurrent mutations in the LAMB3 gene and the population carrier frequency. 1102 79