Browsing by Author "Joseph, PK"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy(JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2003) Waldmuller, S; Sakthivel, S; Saadi, AV; Selignow, C; Rakesh, PG; Golubenko, M; Joseph, PK; Padmakumar, R; Richard, P; Schwartz, K; Tharakan, JM; Rajamanickam, C; Vosberg, HPMutations causing familial hypertrophic cardiomyopathy (HCM) have been described in at least 11 genes encoding cardiac sarcomeric proteins. In this study. three previously unknown deletions have been identified in the human cardiac genes coding for beta-myosin heavy chain (MYH7 on chromosome 14) and myosin-binding protein-C (MYBPC3 on chromosome 11). In family MM, a 3-by deletion in MYH7 was detected to be associated with loss of glutamic acid in position 927 (DeltaE927) of the myosin rod. In two other families (HH and NP, related by a common founder) a 2-bp loss in codon 453 (exon 16) of MYBPC3 was identified as the presumable cause of a translation reading frame shift. Taken together 15 living mutation carriers were investigated. Six deceased family members (with five cases of premature sudden cardiac death (SCD) in families MM and NP) were either obligate or suspected mutation carriers. In addition to these mutations a 25-bp deletion in intron 32 of MYBPC3 was identified in family MM (five carriers) and in a fourth family (MiR, one HCM patient, three deletion carriers). In agreement with the loss of the regular splicing branch point in the altered intron 32, a splicing deficiency was observed in an exon trapping experiment using MYBPC3 exon 33 as a test substrate. Varying disease profiles assessed using standard clinical, ECG and echocardiographic procedures in conjunction with mutation analysis led to the following conclusions: (1) In family MM the DeltaE927 deletion in MYH7 was assumed to be associated with complete penetrance. Two cases of reported SCD might have been related to this mutation. (2) The two families, HH and NP, distantly related by a common founder, and both suffering from a 2-bp deletion in exon 16 of MYBPC3 differed in their average phenotypes. In family NP. four cases of cardiac death were documented, whereas no cardiac-related death was reported from family HH. These results support the notion that mutations in HCM genes may directly determine disease penetrance and severity; however, a contribution of additional, unidentified factors (genes) to the HCM phenotype can-at least in some cases-not be excluded. (3) The deletion in intron 32 of MYBPC3 was seen in two families, but in both its relation to disease was not unequivocal. In addition, this deletion was observed in 16 of 229 unrelated healthy individuals of the population of the South Indian states of Kerala and Tamil Nadu. It was not seen in 270 Caucasians from Russia and western Europe. Hence. it is considered to represent a regional genetic polymorphism restricted to southern India. The association of the deletion with altered splicing in transfected cells suggests that this deletion may create a "modifying gene", which is per se not or only rarely causing HCM. but which may enhance the phenotype of a mutation responsible for disease. (C) 2003 Elsevier Science Ltd. All rights reserved.Item Novel mutations in MYH7 and MYPBC3 of an Indian family causing hypertrophic cardiomyopathy(JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2001)Item Percutaneous transvenous mitral commissurotomy using an Inoue balloon in children with rheumatic mitral stenosis(INTERNATIONAL JOURNAL OF CARDIOLOGY, 1997)Percutaneous transvenous mitral commissurotomy(PTMC) using the Inoue technique was performed in 557 patients with rheumatic mitral stenosis. Of these, 107 were children aged 10-18 years (mean+/-SD 14.5+/-2.3). All patients were symptomatic New York Heart Association (NYHA) Class II(n = 78) and Class III (n = 29). All were in sinus rhythm. Following PTMC, the mitral valve area (MVA increased from 0.73+/-0.18 to 1.7+/-0.53 cm(2) (P<0.001). There was a significant fall in mean transmitral gradient from 15.6+/-5.2 to 5.1+/-2.3 mmHg, and in mean pulmonary artery pressure from 41+/-15 to 28.4+/-10 (P<0.001). Cardiac tamponade developed in one patient. One patient developed severe mitral regurgitation requiring emergency mitral valve replacement. Five patients (4.7%) developed moderate mitral regurgitation. There was no mortality or cerebral embolism in any of the children. Four patients (3.7%) had oximetry evidence of atrial septal defect. Mean mitral valve area and transmitral gradient at 14 months mean follow up was 1.68+/-0.4 cm(2) and 6+/-3.5 mmHg, respectively, and were comparable to the immediate post-PTMC results. Two patients (1.8%) developed restenosis. The immediate haemodynamic results in children were compared to 450 adult patients who underwent PTMC in the same period. The outcome was similar in both groups. Children were found to have significantly higher pulmonary artery pressure compared to adults. We found that PTMC using an Inoue balloon is very effective and safe in children, and consider that it should be the procedure of choice for young patients with symptomatic rheumatic mitral stenosis. (C) 1997 Elsevier Science Ireland Ltd.