講演情報
[OE6-3]先天性QT延長症候群が疑われた症例に同定されたTBX5_TBX3 欠損
○大野 聖子1, 吉永 正夫2 (1.国立循環器病研究センター 分子生物学部, 2.鹿児島医療センター 小児科)
A 9-year-old girl who was diagnosed with long QT syndrome was introduced for the genetic testing. Her heart rate and QTc at rest was 42bpm and 508ms. She had no history of syncope, and repeated Holter ECG detected no ventricular arrhythmia. She had been pointed out cardiac murmur and diagnosed with small patent ductus arteriosus (PDA), small atrial septal defect (ASD) and sick sinus syndrome just after the birth. PDA and ASD were spontaneously closed. At the age of two, subglottis stenosis was found, and tracheotomy was performed. For the genetic testing, we first performed targeted gene sequencing using short read sequencer, however, no pathogenic variant was identified. Using the data by short read sequencer, we performed pair analysis and found a deletion of TBX5. By the comparative genomic hybridization analysis, the deletion range was supposed to be about 1 mega bases including TBX3, and her deletion was NC_000012.11:g.114507136_115497158delinsCT confirmed by long PCR and Sanger methods. TBX3 and TBX5 are ones of T-box genes and work as transcriptional factors. The pathogenic variants in these genes cause Ulnar-Mammary syndrome (UMS) or Holt-Oram Syndrome (HOS) characterized by malformation in upper limbs and congenital heart diseases. Several patients with deletions of these genes have been reported. Their phenotypes are overlapping those of UMS and HOS and variable even in the same family. Here we first report a Japanese patient with the deletion of TBX3 and TBX5. Understanding the genetic background of the patient would be useful for the treatment of the patient.