کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3212643 1203189 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Splicing abnormality of integrin β4 gene (ITGB4) due to nucleotide substitutions far from splice site underlies pyloric atresia-junctional epidermolysis bullosa syndrome
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Splicing abnormality of integrin β4 gene (ITGB4) due to nucleotide substitutions far from splice site underlies pyloric atresia-junctional epidermolysis bullosa syndrome
چکیده انگلیسی


• We disclosed two novel ITGB4 mutations in non-lethal PA-JEB patient.
• The mutations were c.264+2TtoA and c.1762−25TtoA.
• Maternal c.1762−25TtoA was a branch-point mutation.
• Proband showed non-lethal phenotype regardless of both mutations leading PTC.

BackgroundPyloric atresia-junctional epidermolysis bullosa syndrome (PA-JEB) is a rare subgroup of epidermolysis bullosa, which is inherited disorder characterized by skin fragile. PA-JEB is caused by mutation of ITGB4 or ITGA6, which encodes integrin β4 or α6, respectively.ObjectiveTo clarify the molecular basis of PA-JEB and to expand the mutational database, we carried out the mutational analysis of a 29-year-old Japanese PA-JEB patient.MethodsStandard methods were used to prepare, PCR-amplify, and sequence DNA or mRNA in peripheral blood or skin samples, respectively.ResultsSequence analysis revealed two novel mutations in ITGB4, c.264+2TtoA and c.1762−25TtoA. The paternal c.264+2TtoA resided within a splice site consensus region and generated two splice variants resulting in a premature termination codon (PTC). The maternal c.1762−25TtoA was a unique mutation because of its location, 25 bp away from the splice site, and resided in branch-point consensus sequence. This c.1762−25TtoA substitution resulted in generation of two abnormal transcripts each with a PTC. Genotype–phenotype correlation in this case was also unique because the proband showed a non-lethal phenotype regardless of both mutations resulted in only abnormal transcripts with a PTC.ConclusionThe present case expands the mutational database and further elucidates the genotype–phenotype correlation for this rare disease, PA-JEB.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Dermatological Science - Volume 78, Issue 1, April 2015, Pages 61–66
نویسندگان
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