title: Ectopic mineralization disorders of the extracellular matrix of connective tissue: molecular genetics and pathomechanisms of aberrant calcification.
abstract: Ectopic mineralization of connective tissues is a complex process leading to deposition of calcium phosphate complexes in the extracellular matrix, particularly affecting the skin and the arterial blood vessels and common in age-associated disorders. A number of initiating and contributing metabolic and environmental factors are linked to aberrant mineralization in these diseases, making the identification of precise pathomechanistic pathways exceedingly difficult. However, there has been significant recent progress in understanding the ectopic mineralization processes through study of heritable single-gene disorders, which have allowed identification of discrete pathways and contributing factors leading to aberrant connective tissue mineralization. These studies have provided support for the concept of an intricate mineralization/anti-mineralization network present in peripheral connective tissues, providing a perspective to development of pharmacologic approaches to limit the phenotypic consequences of ectopic mineralization. This overview summarizes the current knowledge of ectopic heritable mineralization disorders, with accompanying animal models, focusing on pseudoxanthoma elasticum and generalized arterial calcification of infancy, two autosomal recessive diseases manifesting with extensive connective tissue mineralization in the skin and the cardiovascular system.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 S. 10th Street, Philadelphia, PA, United States.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 S. 10th Street, Philadelphia, PA, United States.
authors.forename: Qiujie
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 S. 10th Street, Philadelphia, PA, United States. Electronic address: Jouni.Uitto@Jefferson.edu.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D011561:Pseudoxanthoma Elasticum / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D061205:Vascular Calcification / Q000235:genetics / Q000378:metabolism*
keywords: Ectopic mineralization; Generalized arterial calcification of infancy; Heritable connective tissue diseases; Pathomechanisms of mineralization disorders; Pseudoxanthoma elasticum
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