SREE CHITHRA TIRUNAL INSTITUTE FOR MEDICAL SCIENCES TECHNOLOGY

to u frame shin in the heptad repeat pattern. Assuming that the deleted allele is expressedin the myocardium, it is tempting to speculate that the mutation interferes with normalheart muscle set up at the level of MHC dimerization. Abnormal dimerization leads to aless rigid rod and therefore an impaired transmission of the force generated in the myosinhead. Considering it's disruptive nature, E delta 927 mutation is the molecular cause forthe serious type of HCM observed in the proband's family. The glutamic acid in thisposition has been highly conserved phylogenetically in myosin genes from dictylosteiodato man, suggesting an important role for the function of the protein.Second mutation seen in same family was in MYBPC3 in the intron 32. Thisleads to disruption to inability of MYBPC to incorporate into sarcomere at A bands.Patients are less symptomatic and onset clinically was beyond 40 years of age. All adultswith the mutation had LVH. MR was seen in one patient, none had SAM. Echo wise,LVH was concentric in all. All had DOE and history of syncope was present in. onlyone, oCCUlTing at an age beyond 60years. Penetrance is only 50 1 %. In general, thismutation is not expressed at middle age. Delayed expression of disease and favorableoutcome may hinder recognition of heritable nature of mutation in MYBPC3.The patient who had both the mutation is significantly symptomatic. She hasMR, LVOTO, SAM and LV diastolic dysfunction with Cl. III AO E, DOE.ASH,Here;mutation is likely to be additive. This study is in agreement with the conclusion thatdisease expression is more pronounced in patients who had two mutation (6), one inBeta MYHC and other in MYBPC gene. Such a constellation has been reported once inthe literature. ( 7) Similarly until now ;only two compound heterozygous for mutationsin MYH7 gene have been described (5, 6) finding support to the notion that HCM may39