Cardiomyopathy, dilated, 1C is associated with one of six mutation in LDB3 gene: Ile352Met (rs121908336); Thr213Ile (rs121908337),
The213Ile (rs121908337), Asp117Asn (rs121908338), Lys136Met (rs121908339) (PMID:14662268) and Asp626Asn (rs45514002) (PMID:14660611).
Vatta et al. (2003) screened the LDB3 gene in 100 probands with dilated cardiomyopathy (CMD), 15 of whom also had left ventricular noncompaction (LVNC). They identified heterozygous missense mutations in 2 families, one with CMD and left ventricular ... Vatta et al. (2003) screened the LDB3 gene in 100 probands with dilated cardiomyopathy (CMD), 15 of whom also had left ventricular noncompaction (LVNC). They identified heterozygous missense mutations in 2 families, one with CMD and left ventricular hypertrophy (LVH) and the other with CMD, severe LVH, and LVNC (605906.0004 and 605906.0005, respectively), and 4 sporadic patients, 1 with CMD and LVH (605906.0008) and 3 with CMD and LVNC, 1 of whom also had severe LVH (605906.0006 and 605906.0007, respectively). Arimura et al. (2004) analyzed the LDB3 gene in 96 unrelated Japanese patients with dilated cardiomyopathy who were negative for mutation in 11 other cardiomyopathy-associated genes and identified a missense mutation (605906.0009) in a 61-year-old man; his affected brother and sister also carried the mutation as did an unaffected sister. An older brother had died suddenly at age 51 and another brother died of CMD at age 61. Development of disease occurred relatively late in this family: after 50 years of age in the 4 affected brothers, and at 69 years of age in their affected sister. The authors noted that the 65-year-old mutation-positive unaffected sister might yet develop disease. There were no signs of skeletal muscle involvement in these patients and no evidence of a primary conduction defect on electrocardiogram. The mutation was not found in 2 unaffected brothers or in 400 unrelated healthy controls. In 4 affected members of 2 unrelated Japanese families with LVNC, Xing et al. (2006) identified heterozygosity for a 1876G-A transition in exon 15 of LDB3, resulting in the D626N substitution. The mutation was not found in 200 controls. In the first family, twin sisters presented with isolated LVNC shortly after birth; their father and paternal grandfather were reportedly diagnosed with LVNC and dilated cardiomyopathy, but DNA was not available for study. In the second family, the male proband was diagnosed with isolated LVNC and Wolff-Parkinson-White syndrome (WPW; 194200) on routine physical examination at 13 years of age; his asymptomatic mutation-positive mother was found to have LVNC on echocardiography. A maternal aunt died at 10 years of age of indistinct cardiac disease.