1/4. dna based prenatal testing for the skin blistering disorder epidermolysis bullosa simplex.epidermolysis bullosa simplex (EBS) is a skin fragility disorder in which mild physical trauma leads to blistering. The phenotype of the disorder is variable, from relatively mild affecting only the hands and/or feet, to very severe with widespread blistering. For the severest forms of EBS there is a demand for prenatal diagnosis which until now has involved a fetal skin biopsy in the second trimester. The identification of mutations in the genes encoding keratins K5 and K14 as the cause of EBS opens up the possibility of much earlier diagnosis of the disease. We report here four cases in which prenatal testing was performed. In three of the cases the genetic lesions were unknown at the start of the pregnancy, requiring the identification of the causative mutation prior to testing fetal dna. In two of the four cases novel mutations were identified in K14 and in the two remaining families, a previously identified type of mutation was found. Fetal dna, obtained by chorionic villus sampling or amniocentesis, was analysed for the identified mutations. Three of the dna samples were found to be normal; a mutant K14 allele was identified in the fourth case and the pregnancy was terminated. These results demonstrate the feasibility of dna-based prenatal testing for EBS in families where causative mutations can be found.- - - - - - - - - - ranking = 1keywords = sample (Clic here for more details about this article) |
2/4. A new keratin 5 mutation (K199T) in a family with Weber-Cockayne epidermolysis bullosa simplex.A new missense mutation in the keratin 5 gene (KRT5) in a Chinese family with Weber-Cockayne type epidermolysis bullosa simplex is reported. Direct sequencing identified a heterozygous A --> C substitution at nucleotide 596 altering codon 199 of KRT5 from lysine to threonine in all affected family members, but not in the unaffected family members or in 50 unrelated control samples. The mutation is designated K199T. This mutated lysine residue is sited within the 1A domain of keratin 5 and is highly conserved among all type II keratins. The mutation may perturb the alignment of tonofilaments and, as a consequence, result in skin fragility and blistering.- - - - - - - - - - ranking = 1keywords = sample (Clic here for more details about this article) |
3/4. Identification of somatic and germline mosaicism for a keratin 5 mutation in epidermolysis bullosa simplex in a family of which the proband was previously regarded as a sporadic case.epidermolysis bullosa simplex (EBS) is an autosomal-dominant inherited blistering skin disease characterized by intraepidermal blistering due to mechanical stress-induced degeneration of basal keratinocytes. EBS is caused by mutations in either keratin 5 or keratin 14, the major keratins expressed in the basal layer of the epidermis. We experienced a unique EBS-affected family. The proband had a heterozygous 1649delG mutation in the keratin 5 gene and had been reported as a case of de novo mutation, because the mutations were not detected in the parents' dna from blood samples. However, the proband's younger sister was revealed to have the same disease at birth and we found the same mutation in her. We reinvestigated the familial segregation of the 1649delG mutation and it was shown that the mother's dna from hair bulb and buccal cell samples had the 1649delG mutation heterozygously, but her dna from blood samples did not. A careful check on the mother's history disclosed that she had migratory circinate pigmentation in her skin in childhood, which means maternal somatic and germline mosaicism. The demonstration of somatic and gonadal mosaicism in the keratin 5 gene is important for accurate genetic counselling of families with sporadic cases of EBS.- - - - - - - - - - ranking = 3keywords = sample (Clic here for more details about this article) |
4/4. A new mutation in the linker 12 domain of keratin 5 in a Chinese family with Weber-Cockayne epidermolysis bullosa simplex.A previously undescribed missense mutation was detected in the L12 domain of keratin 5 (K5) in a Chinese family with Weber-Cockayne epidermolysis bullosa simplex. Direct sequencing of the PCR products identified a single base substitution (983A-->G) that changes the aspartic acid residue at codon 328 to glycine in all affected family members, while no mutation was observed either in the healthy individual or 50 unrelated control samples. Asp328 of K5 is remarkably conserved among all type II keratins. D328G is the fourth mutation found to affect this residue in K5-related epidermolysis bullosa simplex, indicating the importance of Asp328 for K5 structure and the dramatic effect that fine changes can have on keratin intermediate filament integrity.- - - - - - - - - - ranking = 1keywords = sample (Clic here for more details about this article) |