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- Title
Identification of two rare and novel large deletions in ITGB4 gene causing epidermolysis bullosa with pyloric atresia.
- Authors
Mencía, Ángeles; García, Marta; García, Eva; Llames, Sara; Charlesworth, Alexandra; Lucas, Raúl; Vicente, Asunción; Trujillo‐Tiebas, María José; Coto, Pablo; Costa, Marta; Vera, Ángel; López‐Pestaña, Arantxa; Murillas, Rodolfo; Meneguzzi, Guerrino; Jorcano, José Luis; Conti, Claudio J; Escámez Toledano, María José; Río Nechaevsky, Marcela
- Abstract
Epidermolysis bullosa with pyloric atresia ( EB- PA) is a rare autosomal recessive hereditary disease with a variable prognosis from lethal to very mild. EB- PA is classified into Simplex form ( EBS- PA: OMIM #612138) and Junctional form ( JEB- PA: OMIM #226730), and it is caused by mutations in ITGA6, ITGB4 and PLEC genes. We report the analysis of six patients with EB- PA, including two dizygotic twins. Skin immunofluorescence epitope mapping was performed followed by PCR and direct sequencing of the ITGB4 gene. Two of the patients presented with non-lethal EB- PA associated with missense ITGB4 gene mutations. For the other four, early postnatal demise was associated with complete lack of β4 integrin due to a variety of ITGB4 novel mutations (2 large deletions, 1 splice-site mutation and 3 missense mutations). One of the deletions spanned 278 bp, being one of the largest reported to date for this gene. Remarkably, we also found for the first time a founder effect for one novel mutation in the ITGB4 gene. We have identified 6 novel mutations in the ITGB4 gene to be added to the mutation database. Our results reveal genotype-phenotype correlations that contribute to the molecular understanding of this heterogeneous disease, a pivotal issue for prognosis and for the development of novel evidence-based therapeutic options for EB management.
- Subjects
DELETION mutation; EPIDERMOLYSIS bullosa; ETIOLOGY of diseases; HUMAN abnormalities; SKIN disease genetics; GENETICS
- Publication
Experimental Dermatology, 2016, Vol 25, Issue 4, p269
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.12938