Ploski Rafal, Rydzanicz Malgorzata, Ksiazczyk Tomasz M, Franaszczyk Maria, Pollak Agnieszka, Kosinska Joanna, Michalak Ewa, Stawinski Piotr, Ziolkowska Lidia, Bilinska Zofia T, Werner Bozena
Department of Medical Genetics, Centre of Biostructure, Medical University of Warsaw, Warsaw, Poland.
Department of Pediatric Cardiology and General Pediatrics, Medical University of Warsaw, Warsaw, Poland.
Am J Med Genet A. 2016 Dec;170(12):3241-3248. doi: 10.1002/ajmg.a.37860. Epub 2016 Sep 8.
Restrictive cardiomyopathy is a rare form of pediatric cardiac disease, for which the known genes include MYH7, TNNT2, TNNI3, ACTC1, and DES. We describe a pediatric proband with fatal restrictive cardiomyopathy associated with septal hypertrophy and compound heterozygosity for TNNC1 mutations (NM_003280: p.A8V [c.C23T] and p.D145E [c.C435A]). This association between restrictive cardiomyopathy and TNNC1 mutations was strengthened by prospective observations on the second pregnancy in the family which revealed, in the presence of the same TNNC1 genotype, prenatally diagnosed hypertrophic cardiomyopathy which evolved into restrictive cardiomyopathy, heart failure and death at the age of 9 months. Contrary to previous reports, family and population analyses showed that each of the TNNC1 variants was not pathogenic when present alone. Our results (i) confirm that genetic backgrounds of hypertrophic cardiomyopathy and restrictive cardiomyopathy overlap and (ii) indicate that TNNC1 is a likely novel gene for autosomal recessive restrictive cardiomyopathy. © 2016 Wiley Periodicals, Inc.
限制型心肌病是一种罕见的儿科心脏疾病，已知与之相关的基因包括MYH7、TNNT2、TNNI3、ACTC1和DES。我们描述了一名患有致命性限制型心肌病的儿科先证者，该疾病伴有室间隔肥厚以及TNNC1突变（NM_003280：p.A8V [c.C23T] 和p.D145E [c.C435A]）的复合杂合性。通过对该家族第二次妊娠的前瞻性观察，加强了限制型心肌病与TNNC1突变之间的这种关联，观察结果显示，在相同的TNNC1基因型存在的情况下，产前诊断为肥厚型心肌病，在9个月大时发展为限制型心肌病、心力衰竭并死亡。与之前的报道相反，家族和群体分析表明，每个TNNC1变体单独存在时都不具有致病性。我们的结果（i）证实肥厚型心肌病和限制型心肌病的遗传背景存在重叠，（ii）表明TNNC1可能是常染色体隐性限制型心肌病的一个新基因。© 2016威利期刊公司
