Disease relevance of TMPRSS3

• Consequently, hearing loss due to defective cochlear transmembrane serine protease TMPRSS3 activity is likely to be related to its effect on proneurotrophin cleavage, indicating an action on neurological components of hearing [1].
• Semi-quantitative PCR showed that TADG-12 is overexpressed in 41 of 55 ovarian cancer specimens relative to normal expression, and the variant form, TADG-12V is found at increased levels in 8 of 22 carcinomas examined [2].
• The category which demonstrated a normal sonographic gallbladder, namely a smooth wall and no internal echos, contained a number of false negatives which proved to have either small stone cholelithiasis or extraphepatic ductal obstruction [3].
• The presence of liver cancer was assumed through the irregularity and increased intensity of echos [4].
• The scoring of echos appears to be useful for the early detection and systematic quantitation of the cardiac effects of the progressive pulmonary disease [5].

High impact information on TMPRSS3

• An 8-bp deletion and insertion of 18 monomeric (approximately 68-bp) beta-satellite repeat units, normally present in tandem arrays of up to several hundred kilobases on the short arms of acrocentric chromosomes, causes congenital deafness (DFNB10) [6].
• Our results indicate that in this family the defective gene, DFNB10, is located in a 12-cM region near the telomere of chromosome 21 [7].
• Linkage analysis mapped the disease locus (DFNB8) on the distal long arm of chromosome 21, most likely between D21S212 and D21S1225 with the highest lod score of 7.31 at theta = 0.00 for D21S1575 on 21q22.3 [8].
• A homology search revealed that the human spinesin gene was located at chromosome 11q23 and contained 13 exons, the gene structure being similar to that of TMPRSS3 whose gene is also located on 11q23 [9].
• Of the over 30 reported autosomal recessive nonsyndromic hearing loss (NSHL) loci, the typical phenotype is prelingual non-progressive severe to profound hearing loss with the exception of DFNB8, which displays postlingual onset and DFNB13, which is progressive [10].

Chemical compound and disease context of TMPRSS3

• OBJECTIVE: Profound hearing loss has been observed in patients with a defect in transmembrane serine protease TMPRSS3, the presumed activator of ENaCs [1].
• In these trials, a low-molecular-weight heparin, clivarin and unfractionated heparin (UFH) were used to treat deep-vein thrombosis (CORTES) and for prophylaxis of the orthopedic surgery (ECHOS) [11].

Biological context of TMPRSS3

• The pathogenic mutations were a 1-bp deletion resulting in a frameshift and an amino acid substitution in the LDLRA domain of TMPRSS3 [12].
• Novel missense mutations of TMPRSS3 in two consanguineous Tunisian families with non-syndromic autosomal recessive deafness [13].
• Comparative protein modeling of the TMPRSS3 protease domain predicted that W251C might lead to a structural rearrangement affecting the active site H257 and that P404L might alter the geometry of the active site loop and therefore affect the serine protease activity [13].
• Two loci for nonsyndromic recessive deafness located on chromosome 21q22.3 have previously been reported, DFNB8 and DFNB10 [12].
• Recently the TMPRSS3 gene, which encodes a transmembrane serine protease, was found to be responsible for two non-syndromic recessive deafness loci located on human chromosome 21q22.3, DFNB8 and DFNB10 [13].

Anatomical context of TMPRSS3

• RESULTS: The brachial plexus components were successfully identified in the transverse view as round to oval hypoechoic structures with small internal punctuate echos in all regions examined except the infraclavicular area (visualized in 27% of the cases) [14].
• After TH treatment for 10 days and 2 mo, hemodynamics, echos, myocyte length, histology, and protein expression were assessed [15].
• The left atrium appeared clear of echos in two patients subsequently documented to have a left atrial thrombus weighing 35 and 100 g, respectively, and located within the body of the left atrium [16].
• The two-dimensional echocardiographic features of ruptured papillary muscle included (1) mobile mass of echos attached to normal chordae tendineae in the left ventricle, (2) absent tip of papillary muscle, and (3) mitral valve prolapse [17].
• Small abnormal echos after mitral valve replacement with bileaflet mechanical prostheses: predisposing factors and effect on thromboembolism [18].

Associations of TMPRSS3 with chemical compounds

• Mutation screening of TMPRSS3 revealed two novel missense mutations, W251C and P404L, altering highly conserved amino acids of the serine protease domain [13].
• In the ECHOS study, the selective dopamine agonist nolomirole (CHF1035) showed no benefit in heart failure patients [19].
• In the CORTES study, three randomized groups of patients (n = 312-328) received prophylactic treatment with either UFH or clivarin (o.d. or b.i.d.). In the ECHOS study, there were approximately 600 patients per group [11].
• Echos of the 1959 to 1961 thalidomide disaster are still with us in the form of the continuing appearance, although more rarely, of similarly malformed children [20].
• Prevalence of low HDL-cholesterol in patients with cardiovascular risk factors: the ECHOS (Etude du Cholesterol HDL en Observationnel) French Survey [21].

Other interactions of TMPRSS3

• To determine the contribution of TMPRSS3 mutations in the general congenital/childhood nonsyndromic deaf population we performed mutation analysis of the TMPRSS3 gene in 448 unrelated deaf patients from Spain, Italy, Greece, and Australia who did not have the common 35delG GJB2 mutation [12].
• Four families harboured four novel alleles of TMPRSS3 (988DeltaA = 352stop), otoancorin (1067A > T = D356V) and pendrin (716T > A = V239D and 1001G > T = 346stop) [22].
• We found evidence for linkage to the DFNB8/10 locus in two unrelated consanguineous Tunisian families segregating congenital autosomal recessive sensorineural deafness [13].
• Mutation analysis excluded UBASH3A as being responsible for DFNB10 [23].
• SLC37A1 maps in the refined critical region of the autosomal recessive deafness locus, DFNB10, on 21q22 [24].

Analytical, diagnostic and therapeutic context of TMPRSS3

• A method of performing chemical-shift imaging is described that avoids some of the disadvantages inherent in the techniques which use spin echos and phase encoding [25].
• The effects of the T1 relaxation time on signal strength are discussed for the commonly used imaging techniques "partial saturation" and "inversion recovery." Production of spin echos and the effect of the T2 relaxation time on spin-echo signal strength are also discussed [26].
• In a control group of patients with biventricular hearts, only 1 of 19 (5.3%) contrast echos was weakly positive [27].
• Clinical trials update from the European Society of Cardiology Heart Failure meeting and the American College of Cardiology: darbepoetin alfa study, ECHOS, and ASCOT-BPLA [19].
• Such abnormal echos on M-mode echocardiography could have been mistaken for a mass in the left ventricular chamber [28].

References