McGrath et al. (2012) studied an Iraqi family in which 3 of 8 sibs born to first-cousin parents had inherited skin fragility. The clinical features were apparent from early childhood and consisted primarily of trauma-induced scale crusts and ... McGrath et al. (2012) studied an Iraqi family in which 3 of 8 sibs born to first-cousin parents had inherited skin fragility. The clinical features were apparent from early childhood and consisted primarily of trauma-induced scale crusts and intermittent skin blistering that was mostly secondary to trauma, such as direct injury or adhesive tape, but occasionally appeared spontaneously. Some of the crusted areas were hemorrhagic, and were sometimes accompanied by bruising. Most lesions cleared over several weeks, leaving slightly atrophic scars and moderate postinflammatory hyperpigmentation. Examination revealed mild diffuse mottled hyper- and hypopigmentation on the trunk and proximal limbs. There was no bleeding tendency, no neurologic abnormalities, and no increased incidence of infection. Hair color was normal. No clinical abnormalities were present in the parents or reported in any other relative.
Using DNA from an affected sib with inherited skin fragility from a consanguineous Iraqi family, who was negative for mutation in the KRT5 (148040) and KRT14 (148066) genes, McGrath et al. (2012) performed whole-exome sequencing and identified homozygosity ... Using DNA from an affected sib with inherited skin fragility from a consanguineous Iraqi family, who was negative for mutation in the KRT5 (148040) and KRT14 (148066) genes, McGrath et al. (2012) performed whole-exome sequencing and identified homozygosity for a 1-bp deletion in the EXPH5 gene (612878.0001). Sanger sequencing confirmed the presence and segregation of the mutation in the pedigree, and the mutation was not found in 200 control chromosomes from mixed Iraqi, Iranian, Kuwaiti, and Omani populations. Analysis under the assumption of a fully penetrant autosomal recessive model generated a lod score of 3.157 for the cosegregation.