1/8. Outcome after surgical repair of junctional epidermolysis bullosa-pyloric atresia syndrome: a report of 3 cases and review of the literature.BACKGROUND: Junctional epidermolysis bullosa-pyloric atresia syndrome is recognized as a distinct autosomal recessive entity. Affected infants present with skin fragility and inability to feed due to intestinal obstruction. Despite successful surgical repair of the anatomical defect, the outcome is poor owing to poor feeding, malabsorption, failure to thrive, and sepsis. OBSERVATIONS: In 70 cases of intestinal obstruction and epidermolysis bullosa reported in the medical literature and the 3 reported here, surgical intervention was attempted 51 times. In all except 16 infants, death occurred before age 11 months (mean age, 70 days). Renal involvement and continued failure to thrive accompanied the skin disease in survivors, who ranged in age from 30 days to 16 years (mean age, 4.0 years). CONCLUSIONS: The poor prognosis of this condition must be considered when decisions are made regarding surgical correction. Attempting surgical correction may be warranted in individual circumstances, but withholding surgical intervention and providing palliative support is an acceptable alternative.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |
2/8. Junctional epidermolysis bullosa: a mild variant in two Indian sisters.Two sisters developed a bullous skin disease in early childhood. The disease had features of junctional epidermolysis bullosa but differed clinically from previously recorded variants.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |
3/8. Analysis of the LAMB3 gene in a junctional epidermolysis bullosa patient reveals exonic splicing and allele-specific nonsense-mediated mRNA decay.How splicing, the process of intron removal in pre-messenger rna (mRNA), is carried out with such fidelity in human cells is still not understood, although some general rules are being proposed mainly by in vitro experiments. These rules are currently being redefined by analysis of splicing mechanisms in patients presenting splicing defects. We analysed material of a patient suffering from junctional epidermolysis bullosa, a heritable blistering skin disease. Absence of laminin-5 protein together with hypoplastic hemidesmosomes at the dermo-epidermal junction in the patient's skin was shown by immunohistochemical analysis and immunoelectron microscopy. Subsequent dna analysis revealed heterozygosity for the mutations R635X and 3009C-->T in the LAMB3 gene. The latter did not alter codon translation, but introduced an exonic splice site in exon 20. Interestingly, this exonic splice site, which presented a splice score of only 68.6, was preferentially used by the spliceosome over the wild-type splice site at the exon 20-intron 20 border, which showed a splice score of 92.2. LAMB3 mRNA was still detectable in RT-PCR analysis although the aberrantly spliced mRNA leads to a stop codon in exon 21, 5' of the commonly assumed 3' border for nonsense-mediated mRNA decay. These results describe an exception to the proposed rules of pre-mRNA splicing and rna degradation.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |
4/8. role of elevated alpha-fetoprotein in prenatal diagnosis of junctional epidermolysis bullosa and pyloric atresia.A case of junctional epidermolysis bullosa, Herlitz variant, and pyloric atresia in a 33 weeks' gestation male infant is reported. The second trimester amniotic fluid exhibited elevated concentrations of alpha-fetoprotein and presence of acetylcholinesterase; however, the fetus appeared anatomically normal by multiple high-resolution ultrasound examinations. This case, as well as others previously reported, shows that serious fetal skin disease should be considered as part of the differential diagnosis whenever persistent elevation of alpha-fetoprotein and presence of acetylcholinesterase are found in the amniotic fluid of a fetus that appears anatomically normal by ultrasound. prenatal diagnosis may be established by fetal skin biopsy and extensive prenatal counseling should be offered to families on the basis of the prognosis and severity of this disease.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |
5/8. Genetic basis of lethal junctional epidermolysis bullosa in an affected fetus: implications for prenatal diagnosis in one family.Fetal skin biopsy at 20 weeks' gestation in a woman at risk for a child with the lethal skin-blistering disorder junctional epidermolysis bullosa (Herlitz) confirmed an affected fetus. Genomic dna from the aborted fetus was examined for mutations in laminin 5, a macromolecule involved in adhesion at the dermal-epidermal junction, and a candidate protein in this condition. Polymerase chain reaction (PCR) amplification of exon 10 and parts of the flanking introns of the gene encoding the beta 3 chain of laminin 5 (LAMB3) and subsequent analysis by agarose gel electrophoresis showed a more slowly migrating band in the affected fetus compared with the normal control. Nucleotide sequencing of the abnormal PCR product revealed a homozygous 77 bp duplication within the exon, resulting in a premature termination codon 250 bp downstream from the 3' end of the duplication. Maternal dna was heterozygous for the mutant and wild-type alleles. These findings illustrate the genetic basis of the skin disease in this case and also offer the prospects of a simple, rapid, and reliable first-trimester dna-based prenatal, or even preimplantation, diagnostic test for future pregnancies in this family.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |
6/8. Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia.Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. For this purpose, we first determined the genomic organization of ITGA6, and placed the gene on chromosome 2q by high resolution radiation hybrid mapping. heteroduplex analysis of PCR products containing the individual exons of ITGA6, followed by direct nucleotide sequencing, revealed that the proband was homozygous for a G-to-T transversion in the 1 position of intron 12. This mutation, 1856 1G-->T, affects an invariant base of the 5' donor splice site predicting aberrant splicing involving exon 12. The mutation was verified in the proband's dna by restriction enzyme digestion which also confirmed that the parents were heterozygous carriers of this mutation. Altered expression of alpha6 integrin, which forms a heterodimer with the beta4 subunit at the dermal-epidermal junction, would explain fragility and blistering as a result of minor trauma to the skin.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |
7/8. Novel homozygous and compound heterozygous COL17A1 mutations associated with junctional epidermolysis bullosa.Junctional epidermolysis bullosa is a heritable, heterogeneous blistering skin disease with mechanically induced dermal-epidermal separation, mild skin atrophy, nail dystrophy, and alopecia. Four unrelated junctional epidermolysis bullosa families with different phenotypes were investigated here and four novel mutations associated with the disease were identified. patients 1, 2, and 3 had generalized atrophic benign epidermolysis bullosa, with nonscarring blistering and varying degree of alopecia. Patient 4 had the localisata variant of junctional epidermolysis bullosa, with predominantly acral blistering and normal hair. All patients had mutations in the COL17A1 gene encoding collagen XVII, a hemidesmosomal transmembrane protein. patients 1 and 2 carried homozygous deletions 520delAG and 2965delG, respectively. Patient 3 was compound heterozygous for a missense and a deletion mutation (G539E and 2666delTT), and patient 4 was heterozygous for a known mutation R1226X. The deletions led to premature termination codons and to drastically reduced collagen XVII mRNA and protein levels, consistent with the absence of the collagen in generalized atrophic benign epidermolysis bullosa skin. The missense mutation G539E allowed synthesis of immunoreactive collagen XVII in keratinocytes, but prevented its secretion, thus causing lack of the protein in the skin. The data suggest that different COL17A1 mutations and their combinations can result in a spectrum of biologic and clinical phenotypes of not only generalized atrophic benign epidermolysis bullosa, but also localized junctional epidermolysis bullosa.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |
8/8. Molecular analysis of the human laminin alpha3a chain gene (LAMA3a): a strategy for mutation identification and dna-based prenatal diagnosis in Herlitz junctional epidermolysis bullosa.Mutations in the genes (LAMA3, LAMB3, and LAMC2) encoding the subunit polypeptides of the cutaneous basement membrane zone protein laminin 5 have been reported in different forms of junctional epidermolysis bullosa (JEB), an inherited blistering skin disease. In this study, we present the complete exon-intron organization of the "a" transcript of the laminin alpha3 chain gene, LAMA3a, which is expressed primarily in the skin. We have performed fine-resolution mapping of this gene on chromosome 18q11.2 using a human-hamster radiation hybrid panel. We have also developed a mutation-detection strategy based on the exon-intron structure of LAMA3a. This strategy, based on PCR amplification of genomic sequences, followed by heteroduplex scanning and automated nucleotide sequencing, was used for successful mutation screening in a family with the lethal (Herlitz) type of JEB, and two novel LAMA3 mutations were identified in the proband. The mutations consisted of a single-base pair deletion in LAMA3a exon A11 on the paternal allele, designated 1239delC, and a two-base pair deletion in LAMA3a exon A23 on the maternal allele, designated 2959delGG. This information was also used for dna-based prenatal testing in a subsequent pregnancy in this family. Collectively, these results attest to our expanding capability to elucidate the genetic basis of various forms of epidermolysis bullosa using molecular techniques.- - - - - - - - - - ranking = 1keywords = skin disease (Clic here for more details about this article) |