Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acne vulgaris (AV) affects most adolescents, and of those affected, moderate to severe disease occurs in 20%. Comedones, follicular plugs consisting of desquamated keratinocytes and sebum, are central to its pathogenesis. Despite high heritability in first-degree relatives, AV genetic determinants remain incompletely understood. We therefore employed whole-exome sequencing (WES) in nevus comedonicus (NC), a rare disorder that features comedones and inflammatory acne cysts in localized, linear configurations. WES identified somatic NEK9 mutations, each affecting highly conserved residues within its kinase or RCC1 domains, in affected tissue of three out of three NC-affected subjects. All mutations are gain of function, resulting in increased phosphorylation at Thr210, a hallmark of NEK9 kinase activation. We found that comedo formation in NC is marked by loss of follicular differentiation markers, expansion of keratin-15-positive cells from localization within the bulge to the entire sub-bulge follicle and cyst, and ectopic expression of keratin 10, a marker of interfollicular differentiation not present in normal follicles. These findings suggest that NEK9 mutations in NC disrupt normal follicular differentiation and identify NEK9 as a potential regulator of follicular homeostasis.
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PMID:Somatic Mutations in NEK9 Cause Nevus Comedonicus. 2715 99

Nevus comedonicus syndrome (NCS) is a rare epidermal nevus syndrome characterized by ocular, skeletal, and central nervous system anomalies. We present a 23-month-old boy with a history of a congenital pulmonary airway malformation (CPAM) of the lung and a congenital cataract who developed progressive linear and curvilinear plaques of dilated follicular openings with keratin plugs (comedones) on parts of his scalp, face, and body consistent with nevus comedonicus. MRI of the brain demonstrated an aneurysm of the right internal carotid artery. Genetic testing identified NEK9 c.1755_1757del (p.Thr586del) at mean allele frequency of 28% in the nevus comedonicus. This same mutation was present in the CPAM tissue. This is the first case of a CPAM in a patient with an epidermal nevus syndrome. This case expands the phenotype of nevus comedonicus syndrome to include CPAM and vascular anomalies.
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PMID:Further delineation of the phenotypic spectrum of nevus comedonicus syndrome to include congenital pulmonary airway malformation of the lung and aneurysm. 3196 Oct 58