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Summary Plectin is a 500kDa protein involved in cytoskeleton-plasma membrane attachment with a wide tissue distribution including cutaneous and airway epithelia, muscle and neuronal tissue. Recently, mutations in the gene encoding plectin (PLECI) have been implicated in the pathogenesis of an autosomal recessive variant of epidermolysis bullosa simplex in which cutaneous blistering starting in the neonatal period is associated with muscular dystrophy in later life. In this study, we report two unrelated patients, both of consanguineous parentage, who presented with cutaneous blistering and a hoarse cry from birth. Both experienced inspiratory stridor and respiratory distress, necessitating emergency tracheostomy in one case. Immunoreactivity to monoclonal antibodies against plectin was absent or markedly reduced in skin biopsies from both patients. Electron microscopy revealed a low intraepidermal plane of cleavage and hypoplastic hemidesmosomes with a reduced association with keratin intermediate filaments. Direct sequencing of PLEC1 in each case demonstrated two novel homozygous frameshift deletion mutations. 5069del19 and 5905del2, which both create downstream premature termination codons. Although currently neither patient has symptoms of muscle disease, the identification of mutations in PLEC1 may be predictive for the future development of muscular dystrophy. Recessive epidermolysis bullosa simplex resulting form abnormalities in plectin should be considered in the differential diagnosis of cutaneous blistering, hoarseness and stridor in infancy. more...

There is scant neuropathological information in the child abuse literature; even the best reviews include assumptions based on the findings of a few inadequate early studies. Our recent series of 53 fatal cases (Brain 124 (2001) 1290, 1299 [1,2]) demonstrated age-related patterns of brain injury and showed the substrate of severe encephalopathy in the infants to be hypoxic brain damage, not diffuse traumatic axonal injury ('DAI'), as had previously been thought. About one-third had craniocervical injuries, particularly in the brain stem, suggestive of stretch injury to the neuraxis. Our interpretation was that this finding implied a mechanism of injury--brain stem damage from stretch injury to the neck with resultant apnoea--that could account for the clinical scenario in many cases, and for which violence would not necessarily be required. Since publishing this study we have turned our attention to the subgroup of infants who die without objective signs of injury, such as skull fracture or impact, whose carers are accused of abuse, usually, "violent shaking", on the pathologic findings alone. Given the striking discrepancy that there often is in such cases between the relatively trivial findings in the brain and the accusations of violence, we have been looking at the pathogenesis of the typical intracranial bleeding. A histologic study of dura from 50 paediatric autopsies, none of whom had suffered a head injury, has led us to propose that the subdural and retinal bleeding in such cases may well have a physiological aetiology, rather than being caused directly by trauma. more...

We report that mutation in the gene for plectin, a cytoskeleton–membrane anchorage protein, is a cause of autosomal recessive muscular dystrophy associated with skin blistering (epidermolysis bullosa simplex). The evidence comes from absence of plectin by antibody staining in affected individuals from four families, supportive genetic analysis (localization of the human plectin gene to chromosome 8q24.13–qter and evidence for disease segregation with markers in this region) and finally the identification of a homozygous frameshift mutation detected in plectin cDNA. Absence of the large multifunctional cytoskeleton protein plectin can simultaneously account for structural failure in both muscle and skin. more...