Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Jagged1 mutation analysis in Alagille syndrome patients

Alagille 증후군에서 Jagged1 돌연변이

  • Ko, Jae Sung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Yang, Hye Ran (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Kyung Mo (Department of Pediatrics, University of Ulsan College of Medicine) ;
  • Seo, Jeong Kee (Department of Pediatrics, Seoul National University College of Medicine)
  • 고재성 (서울대학교 의과대학 소아과학교실) ;
  • 양혜란 (서울대학교 의과대학 소아과학교실) ;
  • 김경모 (울산대학교 의과대학 소아과학교실) ;
  • 서정기 (서울대학교 의과대학 소아과학교실)
  • Received : 2006.01.12
  • Accepted : 2006.02.20
  • Published : 2006.05.15
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Abstract

Purpose : Alagille syndrome is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, vertebrae, and craniofacial region. The Jagged1(JAG1) gene, which encodes a ligand of Notch, has been found mutated in Alagille syndrome. The aim of the study was to investigate the mutation analysis of JAG1 gene in Korean patients with Alagille syndrome. Methods : Genomic DNA was extracted from peripheral leukocytes of 6 patients. The 26 exons of JAG1 gene were amplified and PCR products were directly sequenced. Results : Two novel frameshift mutations were found. 118delC in exon 2 was found in a patient who developed hepatocellular carcinoma at 4 years of age. 999-1000delTG was identified in exon 7. Conclusion : Mutations identified in this study are expected to give rise to truncated proteins.

목 적 : Alagille 증후군은 간, 심장, 눈, 척추, 얼굴 모양 등 여러 장기에 이상을 일으키며 상염색체 우성으로 유전되는 질환이다. Alagille 증후군의 유전자인 JAG1은 Notch 수용체에 대한 리간드를 만든다. 이 연구의 목적은 우리나라 Alagille 증후군 환자에서 JAG1 유전자의 돌연변이를 찾아내는 것이다. 방 법 : Alagille 증후군으로 확진 받은 6명의 말초혈액 백혈구에서 DNA를 추출하여 JAG1 유전자에 대하여 중합효소연쇄 반응 및 정제 후 직접 염기서열 분석하였다. 결 과 : 2개의 새로운 frameshift 돌연변이가 발견되었다. 4세에 간세포암이 발생한 환자에서 엑손 2에서 118delC이 발견되었다. 한 환자에서는 엑손 7에서 999-1000delTG이 발견되었는데, 2개 돌연변이들은 정지코돈을 만들었다. 결 론 : 우리나라 Alagille 증후군 환자에서 단백이 잘라져 기능을 못하는 frameshift 돌연변이를 찾아내었다.

Keywords

Acknowledgement

Supported by : 서울대학교병원

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