AB046. X-linked dilated cardiomyopathy: the dystrophinopathy in a Thai family
Thanyachai Sura1, Thossaporn Morasert1, Polawat Khemthong1, Atchara Tunteeratum1, Kanchit Likitthanasombat2, Donniphat Dejsuphong3, Jakris Eu-ahsunthornwattana1
Background: Idiopathic dilated cardiomyopathy generally presents with congestive heart failure secondary to an increase in ventricular size and impairment of ventricular function. It is one of the leading causes of cardiovascular morbidity and mortality. Most cases have been considered to be sporadic, but recent studies have demonstrated that up to 20% of cases may be inherited, suggesting a strong genetic component for this group of diseases. Inheritance patterns vary and may be X-linked, autosomal dominant, or autosomal recessive. Dystrophin gene defect is one of the known causes of the X-linked dilated cardiomyopathy (XLDCM).
Case report: We reported a Thai 19-year-old young man, an elder brother of two brothers and three sisters, who was referred from a general hospital with pneumonia and congestive heart failure. The patient was later proved having dilated cardiomyopathy with low ejection fraction (EF =20%). He previously had normal motor power and was noticed that his calves muscle was enlarged. The muscle enzyme was elevated, creatine phosphokinase (CPK) =9,772 IU/L, CK-MB =191 IU/L and troponin T (TnT) =0.25 mcg/L. He eventually passed away in the third day of admission in the cardiac care unit (CCU). His parents are first cousin to each other. Both of his father and grandfather died with heart disease in the fourth decade of their lives. He was, then diagnosed as XLDCM.
Results: The DNA of the patient was tested for dystrophin gene deletions by multiplex PCR and MLPA techniques which gave the negative results. The DNA sequencing was performed at the 5' portion of the gene, including the muscle promoter, exon 1, and the exon 1-intron 1 splice site. A missense mutation in exon 9 at nucleotide 1043 was identified that causes an alanine to be substituted for threonine, a highly conserved amino acid, at position 279 (T279A). This mutation results in destabilizing the protein. The T279A mutation of the dystrophin gene, then was tested in all of his brothers and sisters which four of them have the same mutation and expressed the spectrum of cardiomyopathy phenotype.
Keywords: X-linked dilated cardiomyopathy (XLDCM); dystrophinopathy
