Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene which encodes a protein expressed in the apical membrane of exocrine epithelial cells. CFTR functions principally as a cAMP-induced chloride channel and appears capable of regulating other ion channels. Besides the most common mutation, DeltaF508, accounting for about 70% of CF chromosomes worldwide, more than 850 mutant alleles have been reported to the CF Genetic Analysis Consortium. These mutations affect CFTR through a variety of molecular mechanisms which can produce little or no functional CFTR at the apical membrane. This genotypic variation provides a rationale for phenotypic effects of the specific mutations. The extent to which various CFTR alleles contribute to clinical variation in CF is evaluated by genotype-phenotype studies. These demonstrated that the degree of correlation between CFTR genotype and CF phenotype varies between its clinical components and is highest for the pancreatic status and lowest for pulmonary disease. The poor correlation between CFTR genotype and severity of lung disease strongly suggests an influence of environmental and secondary genetic factors (CF modifiers). Several candidate genes related to innate and adaptive immune response have been implicated as pulmonary CF modifiers. In addition, the presence of a genetic CF modifier for meconium ileus has been demonstrated on human chromosome 19q13.2. The phenotypic spectrum associated with mutations in the CFTR gene extends beyond the classically defined CF. Besides patients with atypical CF, there are large numbers of so-called monosymptomatic diseases such as various forms of obstructive azoospermia, idiopathic pancreatitis or disseminated bronchiectasis associated with CFTR mutations uncharacteristic for CF. The composition, frequency and type of CFTR mutations/variants parallel the spectrum of CFTR-associated phenotypes, from classic CF to mild monosymptomatic presentations. Expansion of the spectrum of disease associated with the CFTR mutant genes creates a need for revision of the diagnostic criteria for CF and a dilemma for setting nosologic boundaries between CF and other diseases with CFTR etiology. (+info)
Eccrine angiomatous hamartoma with elements of an arterio-venous malformation: a newly recognized variant.
We present the case of a 54-year-old man with a brown-red nodule on the hand that had been present since early adulthood. Histology of the excisional biopsy revealed hyperplasia and proliferation of eccrine, apocrine, lipomatous, and vascular structures. These findings were most characteristic of the entity known as eccrine angiomatous hamartoma (EAH), an uncommon tumor that may present variable clinical and histological features. In addition, this particular case exhibited a prominent component of arterio-venous malformation that distinguishes it from other EAHs described in the literature and adds to the spectrum of histologic findings that can be seen with this entity. (+info)
Late-onset porokeratotic eccrine ostial and dermal duct nevus associated with sensory polyneuropathy and hyperthyroidism.
A 38-year-old man presented with a chief complaint of blue-speckled secretions on his cheeks, brought on by exertion. Based on the clinical features, a diagnosis of apocrine chromhidrosis was made. Histopathologic exam further supported this diagnosis. Possible treatment options for apocrine chromhidrosis are discussed. (+info)
Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?