Allergen-specific immunotherapy with apples: selected cultivars could be a promising tool for birch pollen allergy.

BACKGROUND: Most birch pollen-allergic patients develop allergic cross-reactions to the major allergen found in apples Mal d1, known as pollen-related food allergy (prFA). This is due to a strong clinically relevant homology between the major allergen in birch Bet v 1 and Mal d 1. Daily apple consumption induces oral tolerance in prFA, but its effect on the inhalational allergy has not been investigated. OBJECTIVES: As continuous apple consumption might also mitigate the inhalational allergy, this study aimed to uncover apple cultivars suitable for treatment of birch pollen rhinoconjunctivitis and apple allergy in a controlled and established dosage. METHODS: Patients (n = 52) with birch pollen allergy and prFA to apples were subjected to a prick-to-prick test (SPT) with 23 cultivars (red-fleshed, old traditional and new commercial). By SPT, the apple parts flesh, peel equatorial and peel apical near the stalk were compared for their reactivity. One apple cultivar of each allergenicity class (low, middle and high) was subsequently tested in an oral provocation test (OPT). RESULTS: According to the SPTs, we provide a ranking of all 23 cultivars. Red-fleshed apples displayed the lowest reactivity, followed by old and new cultivars. Four cultivars showed disagreement from their allergenicity class: Santana and Pink Lady®, new cultivars that provoked only low to moderate. In contrast, White Rosemary and Goldparmäne, two old cultivars, induced strong reactions. Skin reactivity increased from flesh to peel to stalk, and SPT results could predict the severity of prFA of each allergenicity class. CONCLUSIONS: Herein, we propose a treatment protocol for allergen immunotherapy to birch pollen and prFA with daily apple consumption. Red-fleshed, old and the new cultivars Santana and Pink Lady® provoke less allergic reactions and are suitable for initial induction. After a controlled and well-tolerated increase of intake, also moderate and finally high allergenic apple cultivars should be integrated into treatment of birch pollen allergenic patients.

A founder synonymous COL7A1 mutation in three Danish families with dominant dystrophic epidermolysis bullosa pruriginosa identifies exonic regulatory sequences required for exon 87 splicing.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) (OMIM 604129) represents a distinct variant within the DEB clinical spectrum. It is characterized by intense pruritus and distinctive nodular prurigo-like and/or hypertrophic lichenoid lesions mainly localized on the arms, legs and upper shoulders. DEB-Pr is caused by either dominant (DDEB-Pr) or recessive mutations in the COL7A1 gene encoding type VII collagen (COLVII). The full spectrum of COL7A1 mutations in DEB-Pr remains elusive and the genotype-phenotype correlation is largely incomplete. Here, we report and functionally characterize a previously unrecognized translationally silent exonic COL7A1 mutation that results in skipping of exon 87 and is associated with DDEB-Pr phenotypes in several members of three apparently unrelated Danish families. A haplotype segregation study suggested a common ancestor in these kindred. Functional splicing analysis of the mutant exon by a COL7A1 minigene construct and computational prediction for splicing regulatory cis-sequences prove that the mutation alters the activity of an exonic splicing enhancer (ESE) critical for exon inclusion. These findings substantiate for the first time the involvement of an ESE mutation in the pathogenesis of DEB and have implications for genetic counselling of Danish families with DDEB.

Lethal autosomal recessive epidermolytic ichthyosis due to a novel donor splice-site mutation in KRT10.

Epidermolytic ichthyosis (EI; MIM 113800), previously named bullous congenital ichthyosiform erythroderma or epidermolytic hyperkeratosis, is a rare and clinically variable defect of cornification characterized by generalized erythema, erosions, scaling and easily breaking blisters that become less frequent later in life while hyperkeratosis increases. EI is caused by dominant mutations in either KRT1 or KRT10, encoding keratin 1 (K1) and keratin 10 (K10), respectively. Usually, mutations are missense substitutions into the highly conserved α-helical rod domains of the proteins. However, three inbred pedigrees in which EI is transmitted as a recessive trait due to KRT10 null mutations have been described.

Trisomic rescue causing reduction to homozygosity for a novel ABCA12 mutation in harlequin ichthyosis.

Harlequin ichthyosis (HI) is the most severe and often lethal form of congenital ichthyosis, characterized by abnormal desquamation and extreme skin thickening and hardening over the entire body. It is caused by recessive loss-of-function mutations in the ABCA12 gene located on chromosome 2q34. Here, we report a sporadic HI patient born prematurely due to severe growth delay and oligohydramnios. The diagnosis was confirmed by ABCA12 molecular analysis, which disclosed the novel homozygous mutation p.R287X. Microsatellite analysis and parental segregation study showed that the disease resulted from complete paternal isodisomy. In addition, chorionic villus karyotyping revealed a non-mosaic chromosome 2 trisomy, while postnatal peripheral blood karyotype resulted normal female. Thus, these findings indicate that trisomic rescue is one step of the mutational cascade leading to reduction to homozygosity for the ABCA12 mutation in the embryo. Our case is the first reported HI patient in whom the disease is due to uniparental isodisomy.