Moric Ewa, Mazurek Urszula, Połońska Joanna, Domal-Kwiatkowska Dorota, Smolik Sławomir, Kozakiewicz Krystyna, Tendera Michał, Wilczok Tadeusz
Department of Molecular Biology, Biochemistry and Biopharmacy, Medical University of Silesia, ul. Narcyzów 1, 41-200 Sosnowiec, Poland.
J Appl Genet. 2003;44(1):103-9.
Familial hypertrophic cardiomyopathy has a complex multigenic background. Previous work allowed to determine one of the gene loci responsible for this disease on chromosome 14 band q11-q12, and linked it to the alpha and beta-cardiac myosin heavy chains. In this study we demonstrate changes in exon 21, coding for beta-myosin heavy chain. We described 4 patients from different families with an unequivocal diagnosis of hypertrophic cardiomyopathy based on the clinical picture. Direct sequencing of exon 21 revealed the presence of 5 novel mutations. Two of the mutations in codons 771 and 781 revealed in our study did not result in any changes in amino acid sequence. The next three were as follows: in codon 782 (AGC > GAC) transition responsible for Ser-->Asp substitution; in codon 779 (GAG > TAG) mutation that results in replacement of Glu-->Stop; in codon 774 (GAG > GTG) which is expressed as substitution of Glu-->Val. These mutations are located close to mutations identified and described in the literature, so they are likely to cause similar symptoms.
家族性肥厚型心肌病具有复杂的多基因背景。先前的研究已确定14号染色体q11 - q12区域的一个基因座与该病相关，并将其与α和β心肌肌球蛋白重链联系起来。在本研究中，我们展示了编码β - 肌球蛋白重链的第21外显子的变化。我们描述了来自不同家族的4例患者，根据临床表现明确诊断为肥厚型心肌病。对第21外显子进行直接测序发现了5个新的突变。我们研究中发现的密码子771和781的两个突变并未导致氨基酸序列发生任何变化。接下来的三个突变如下：密码子782处的（AGC > GAC）转换导致丝氨酸替换为天冬氨酸；密码子779处的（GAG > TAG）突变导致谷氨酸替换为终止密码子；密码子774处的（GAG > GTG）突变表现为谷氨酸替换为缬氨酸。这些突变位于文献中已鉴定和描述的突变附近，因此它们可能会导致相似的症状。
