elastin and Hearing-Loss--Sensorineural

Lysyl oxidase like 3 (LOXL3) is a copper-dependent amine oxidase responsible for the crosslinking of collagen and elastin in the extracellular matrix. LOXL3 belongs to a family including other members: LOX, LOXL1, LOXL2, and LOXL4. Autosomal recessive mutations are rare and described in patients with Stickler syndrome, early-onset myopia and non-syndromic cleft palate. Along with an essential function in embryonic development, multiple biological functions have been attributed to LOXL3 in various pathologies related to amino oxidase activity. Additionally, various novel roles have been described for LOXL3, such as the oxidation of fibronectin in myotendinous junction formation, and of deacetylation and deacetylimination activities of STAT3 to control of inflammatory response. In tumors, three distinct roles were described: (1) LOXL3 interacts with SNAIL and contributes to proliferation and metastasis by inducing epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells; (2) LOXL3 is localized predominantly in the nucleus associated with invasion and poor gastric cancer prognosis; (3) LOXL3 interacts with proteins involved in DNA stability and mitosis completion, contributing to melanoma progression and sustained proliferation. Here we review the structure, function and activity of LOXL3 in normal and pathological conditions and discuss the potential of LOXL3 as a therapeutic target in various diseases.

Topics: Amino Acid Oxidoreductases; Arthritis; Cleft Palate; Collagen; Connective Tissue Diseases; Elastin; Epithelial-Mesenchymal Transition; Extracellular Matrix; Gene Expression Regulation; Hearing Loss, Sensorineural; Humans; Isoenzymes; Myopia; Neoplasms; Organ Specificity; Retinal Detachment; Signal Transduction; Snail Family Transcription Factors; STAT3 Transcription Factor

Topics: Adolescent; Blood Platelet Disorders; Child; Elastin; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Hearing Loss, Sensorineural; Humans; Male; Myosin Heavy Chains; Pedigree; Platelet Aggregation; Rare Diseases; Sampling Studies; Sweat Glands; Syndrome; Thrombocytopenia; Young Adult

Williams syndrome (WS) has long been known as a complex disorder of dysmorphic facial features, described as elfin face, mental retardation or learning disability, loquacious personality, and supravalvular aortic stenosis. The etiology is now known to be due to deletion of the elastin gene (ELN) on long arm of chromosome 7. Thai patients were previously reported by clinical diagnosis. This study reports the first two cases of WS with ELN deletion diagnosed by fluorescent in situ hybridization (FISH) technique. Clinically, hyperacusis is a common finding in WS associated with otitis media. Neither of the patients had hyperacusis, but one of them had bilateral sensorineural hearing loss, which to our knowledge, has never been reported.

Topics: Elastin; Female; Gene Deletion; Hearing Loss, Sensorineural; Humans; In Situ Hybridization, Fluorescence; Infant; Thailand; Williams Syndrome