Long-term Follow-up of a Spontaneously Improving Patient with Junctional Epidermolysis Bullosa Associated with ITGB4 c.3977-19T&gt;A Splicing Mutation

Diociaiuti, Andrea; Castiglia, Daniele; Morini, Francesco; Boldrini, Renata; Fortugno, Paola; Zambruno, Giovanna; Hachem, May El

doi:10.2340/00015555-1381

Cited by 16 publications

(15 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Secondary modifiers may account for the phenotypic variability of this EB subtype . According to the current EB classification, EB‐PA is associated with death in many cases (+3 and +4 subsequently on a 0 to +4 scale); however, this study and others report an increasing number of patients with nonlethal forms.…”

Section: Discussionmentioning

confidence: 65%

“…Yellow asterisks mark combination with very mild skin effects. 24 Interestingly, in two cases, severe urinary tract symptoms were transient and resolved within 2 years (patients 3 and 4). Therefore, paediatricians and especially paediatric urologists should be aware of the possibility that urinary tract problems in association with minor skin blistering may represent a genetic disorder caused by a6b4 integrin mutations.…”

Section: Discussionmentioning

confidence: 94%

“…Our findings are consistent with a recent report by Diociaiuti et al . presenting urinary tract involvement in combination with very mild skin effects . Interestingly, in two cases, severe urinary tract symptoms were transient and resolved within 2 years (patients 3 and 4).…”

Section: Discussionmentioning

confidence: 94%

See 2 more Smart Citations

Phenotypic spectrum of epidermolysis bullosa associated with α6β4 integrin mutations

et al. 2013

View full text Add to dashboard Cite

SummaryBackground Integrin a6b4 is a transmembrane receptor and a key component of the hemidesmosome anchoring complex. It is involved in cell-matrix adhesion and signalling in various tissues. Mutations in the ITGA6 and ITGB4 genes coding for a6b4 integrin compromise dermal-epidermal adhesion and are associated with skin blistering and pyloric atresia (PA), a disorder known as epidermolysis bullosa with PA (EB-PA). Objectives To elucidate the molecular pathology of skin fragility in eight cases, disclose the underlying ITGA6 and ITGB4 mutations and study genotype-phenotype correlations. Methods DNA was isolated from ethylenediaminetetraacetic acid-blood samples, and the coding exons and exon-intron boundaries of ITGA6 and ITGB4 were amplified by polymerase chain reaction (PCR), and directly sequenced. Skin samples were submitted to immunofluorescence mapping with antibodies to adhesion proteins of the dermal-epidermal junction. Primary keratinocytes were isolated, and used for RNA and protein extraction, reverse transcription PCR and immunoblotting. Ultrastructural analysis of the skin was performed in one patient. Results We disclose 10 novel mutations, one in ITGA6 and nine in ITGB4. Skin cleavage was either intraepidermal or junctional. Lethal outcome and PA correlated with loss-of-function mutations in two cases. Solely mild skin involvement was associated with deletion of the C-terminus of b4 integrin. Combinations of missense, nonsense or frameshift mutations caused severe urinary tract involvement in addition to skin fragility in five cases. Conclusions The present study reveals novel ITGA6 and ITGB4 gene mutations and supports previous reports showing that the phenotype may lack PA and be limited to skin and nail involvement. In four out of six cases of EB-PA, life expectancy was not impaired. A high frequency of urinary tract involvement was found in this study, and represented the main cause of morbidity. Low levels of b4 integrin expression were compatible with hemidesmosomal integrity and a mild skin phenotype.

show abstract

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Phenotypic spectrum of epidermolysis bullosa associated with α6β4 integrin mutations

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Of the 66 mutations reported to date in ABCA12 , more than half alter conserved residues, while the rest affect either consensus splice sites or consist of small deletions/insertions. A substantial number of exceptional mutational events leading to abnormal splicing have previously been shown to underlie the pathogenesis of several genodermatoses and other syndromes affecting the skin amongst other organs . In the present study, we report the first instance of a case of ARCI resulting from a synonymous mutation leading to aberrant splicing.…”

Section: Discussionmentioning

confidence: 62%

The sound of silence: autosomal recessive congenital ichthyosis caused by a synonymous mutation in ABCA12

Goldsmith

Fuchs-Telem

Israeli

et al. 2013

Experimental Dermatology

View full text Add to dashboard Cite

Autosomal recessive congenital ichthyosis refers to a heterogeneous group of cornification disorders of major impact on patients' life. The disease has been linked so far to mutations in 8 distinct genes. We report a consanguineous family of Arab Muslim origin with several members displaying a severe form of congenital ichthyosiform erythroderma. Using a panel of polymorphic microsatellite markers, we identified a region of homozygosity shared by all patients on 2q34, in a region harbouring the ABCA12 gene. Direct sequencing of genomic DNA derived from a patient failed to reveal any obviously pathogenic change in the coding sequence of this gene. In contrast, cDNA sequence analysis revealed the existence of a 163-bp-long deletion in exon 24, thus pointing to a splicing defect. Careful reanalysis of the genomic DNA sequence revealed apart from several known single-nucleotide polymorphisms, a hitherto unreported homozygous synonymous mutation in exon 24 (c.3456G>A; p.S1152S), which was found to lead to the formation of a novel splicing acceptor site. Synonymous mutations have been shown to uncommonly cause inherited disorders in humans. Here, we present the first example of a congenital form of ichthyosis resulting from such a genetic defect.

show abstract

“…Generalized enamel hypoplasia has been reported in 59 case reports of individuals with JEB, 2,25,27–45 as well as 100% of the patients with JEB in a series of cases ( n = 6 severe JEB‐H, n = 19 other types of JEB) (Images 2.3 and 2.4). 46 Enamel hypoplasia can be observed in panoramic radiographs as teeth with thin, abnormal, severely dystrophic enamel formation (Image 2.5).…”

Section: Chapter 2: Oral Manifestations Of Epidermolysis Bullosa: Sysmentioning

confidence: 99%

Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa

Krämer

Lucas

Gamboa

et al. 2020

Special Care in Dentistry

View full text Add to dashboard Cite

Background: Inherited epidermolysis bullosa (EB) is a genetic disorder characterized by skin fragility and unique oral features. Aims: To provide (a) a complete review of the oral manifestations in those living with each type of inherited EB, (b) the current best practices for managing oral health care of people living with EB, (c) the current best practices on dental implant-based oral rehabilitation for patients with recessive dystrophic EB (RDEB), and (d) the current best practice for managing local anesthesia, This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

Long-term Follow-up of a Spontaneously Improving Patient with Junctional Epidermolysis Bullosa Associated with ITGB4 c.3977-19T>A Splicing Mutation

Cited by 16 publications

References 9 publications

Phenotypic spectrum of epidermolysis bullosa associated with α6β4 integrin mutations

Phenotypic spectrum of epidermolysis bullosa associated with α6β4 integrin mutations

The sound of silence: autosomal recessive congenital ichthyosis caused by a synonymous mutation in ABCA12

Clinical practice guidelines: Oral health care for children and adults living with epidermolysis bullosa

Contact Info

Product

Resources

About