Uniparental Disomy of Chromosome 2 Unmasks New ITGA6 Recessive Mutation and Results in a Lethal Junctional Epidermolysis Bullosa in a Newborn

1https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3313 Epidermolysis bullosa (EB) is a group of genetic disorders characterized by fragility of skin and mucosa. The majority of subtypes of EB result from malfunction of anchor proteins of the basal membrane zone (BMZ). Based on the level of blister formation, EB is classified into 4 major forms: EB simplex, junctional EB, dystrophic EB, and Kindler syndrome (Fig. S11). Junctional EB (JEB) is caused by mutations in genes encoding for components of the lamina lucida, e.g. integrin beta 4 (ITGB4), integrin alpha 6 (ITGA6), laminin-332 genes (LAMA3, LAMB3 and LAMC2), etc. One specific type of JEB with mutations in α6β4 integrin presents with skin fragility in association with pyloric atresia. JEB is inherited only in a recessive manner. Trisomy 2 mostly results in first trimester pregnancy loss; it is compatible with life exclusively in mosaic states or when restricted to the placental tissues. Common in utero indications of mosaic trisomy 2 are oligohydramnios and poor foetal growth. High trisomic levels in placenta and the foetus can result in abnormal and fatal phenotypes (1). Phenotypes of uniparental disomy of chromosome 2 (UPD2) resulting in trisomy mosaicism have described phenotypes, such as genital hypoplasia, intrauterinal growth retardation (IUGR) and oligohydramnios. Exceptional cases of full UPD2 have been described in healthy individuals (2, 3). We report here a case of a newborn with JEB resulting from a previously unknown homozygous mutation leading to a premature termination codon in the gene encoding for ITGA6. The loss of heterozygosity occurred in the setting of an exclusive maternal UPD2.