SummaryBackgroundGermline mutations in the tumour suppressor gene CYLD are recognized to be associated with the development of multiple cutaneous cylindromas. We encountered such a patient who presented with breathlessness because of multiple pulmonary cylindromas.ObjectivesTo search for clinical and radiological features of multiple pulmonary cylindromas in a cohort of 16 patients with CYLD mutations.MethodsA retrospective case‐note review was carried out in a tertiary dermatogenetics clinic where CYLD mutation carriers are reviewed on an annual basis. In‐depth investigation was carried out for patients with pulmonary tumours.ResultsFour patients had radiological imaging of their lungs, of which two had multiple pulmonary cylindromas that were confirmed histologically. Serial computed tomography monitoring allowed for pre‐emptive endobronchial laser ablation, preventing major airway obstruction and pulmonary collapse.ConclusionsPulmonary cylindromas are an unrecognized, but infrequently symptomatic, aspect of the phenotype in these patients that can have implications for patient care. They should be considered in patients with a high tumour burden that present with respiratory symptoms, and where appropriate, monitored with serial imaging.
BackgroundClusters of rare cylindroma or spiradenoma tumors are a recurrent clinical presentation, yet conventional genetic testing results in individuals with these tumors are frequently normal.ObjectiveTo determine if genetic mosaicism accounts for such cases.MethodsA study of 6 cases from a series of 55 patients who met criteria for diagnostic gene testing for pathogenic CYLD variants over a 5-year period (2012-2017) was performed. A novel genetic assay was used to study DNA from peripheral blood leukocytes and, where possible, matched skin and tumor tissue.ResultsTwo patients had mosaic pathogenic CYLD variants in both the blood and skin. One of these patients transmitted a pathogenic variant to her daughter, and we report the novel phenotype of a contiguous gene deletion syndrome involving CYLD. Two patients had recurrent pathogenic variants in skin tumors from a single cluster but none detectable in the blood.LimitationsThe remaining 2 patients had clinical features of mosaicism, but these cases were not solved with the assays used because of a lack of access of fresh tumor tissue.ConclusionGenetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients.
Allergic disorders are among the most common diseases around the world especially in children. Many factors contribute to the pathogenesis of atopic disorders, but early events during the pregnancy are very important. The aim of this study was to evaluate the level of cord blood immunoglobulin E (CB-IgE) and its association with maternal in a group of Iranian newborns. In a crosssectional study, 163 pregnant women randomly selected and information about pregnancy and atopy were taken by questionnaire. Blood samples of mothers and matched cord blood were collected and total serum IgE levels were measured by enzyme-linked immunosorbent assay (ELISA) method. To rolling out the possibility of contamination with maternal blood, total IgA was checked for all the cord blood samples. Sixteen percent of mothers had the history of atopic diseases and the mean IgE level was significantly higher in an atopic than nonatopic mothers (241 vs 102, P < 0.001). About 73.9% of cord blood samples, had high IgE level (>0.9 IU/mL). The level of cord blood IgE (CB-IgE) was not significantly different in male and female newborns (2.14 vs 2.15 IU/mL). There was no significant correlation between maternal factors such as age, pregnancy variables, allergens exposure, smoking, and maternal IgE with cord blood IgE.The results of this study showed that CB-IgE is high in a remarkable number of samples; independent of maternal or fetal factors. Further studies need to evaluate the reasons for the high level of IgE in cord blood in our area. K E Y W O R D S allergic predisposition, cord blood immunoglobulin E, Iranian newborns, maternal exposure, sensitization
The routine diagnosis of heritable skin and connective tissue disorders is complicated by the fact that in this group of disorders, clinical manifestations may result from genetic or phenotypic heterogeneity and the existence of new genes and/or novel disease subtypes. Autozygosity mapping (AM) has been proven to be a useful adjunct in the molecular diagnosis of homozygous autosomal recessive (AR) diseases. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using genomewide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases (84.7%) were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analyzed with an EB-targeted next-generation sequencing (NGS) panel. This approach identified mutations in five additional cases, initially undiagnosed due to presence of compound heterozygosity, deep intronic mutations, or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 out of 46 cases (95.7%) diagnosed genetically. The yield of 84.7% using AM-guided sequencing was remarkably similar to that of the independent use of our previously reported NGS targeted panel, in which potential causative variants were identified in 76 of 91 (83.5%) families with EB. Thus, AM is an expedient and cost efficient approach to identify mutated genes consanguineous families.
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