Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Transient neonatal diabetes mellitus with macroglossia diagnosed by methylation specific PCR (MS-PCR)

메틸화 특이 PCR로 진단된 거설증을 동반한 일과성 신생아 당뇨병

  • Jin, Hye Young (Division of Pediatric Endocrinology and Metabolism, Department of Pediatric, University of Ulsan College of Medicine) ;
  • Choi, Jin-Ho (Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Ulsan College of Medicine) ;
  • Kim, Gu-Hwan (Medical Genetics Clinic & Laboratory, Asan Medical Center Children's Hospital University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics,Medical Genetics Clinic & Laboratory, Asan Medical Center Children's Hospital University of Ulsan College of Medicine)
  • 진혜영 (울산대학교 의과대학 소아과학교실) ;
  • 최진호 (울산대학교 의과대학 소아과학교실) ;
  • 김구환 (서울아산병원 의학유전학 클리닉) ;
  • 유한욱 (울산대학교 의과대학 소아과학교실,서울아산병원 의학유전학 클리닉)
  • Received : 2009.07.15
  • Accepted : 2010.02.18
  • Published : 2010.03.15
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Abstract

Transient neonatal diabetes mellitus (TNDM) has been associated with paternal uniparental isodisomy of chromosome 6, paternally inherited duplication of 6q24, or a methylation defect at a CpG island of the ZAC or HYMAI gene. We experienced a case of TNDM in which the patient presented with hyperglycemia, macroglossia, and intrauterine growth retardation, caused by a paternally derived HYMAI. An 18-day-old female infant was admitted to the hospital because of macroglossia and recurrent hyperglycemia. In addition to the macroglossia, she also presented with large fontanelles, micrognathia, and prominent eyes. Serum glucose levels were 200-00 mg/dL and they improved spontaneously 2 days after admission. To identify the presence of a maternal methylated allele, bisulfite-treated genomic DNA from peripheral blood was prepared and digested with BssHII after polymerase chain reaction (PCR) amplification with methylation-specific HYMAI primers. PCR and restriction fragment length polymorphism analysis showed that the patient had only the paternal origin of the HYMA1 gene. TNDM is associated with a methylation defect in chromosome 6, suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype.

일과성 신생아 당뇨병은 6번 염색체의 부친 이체성, 부친으로부터 유래한 염색체 6q24의 중복, ZAC 또는 HYMAI 유전자의 CpG 섬의 메틸화 결함에 의해 야기된다. 저자들은 고혈당, 거설증, 자궁내성장지연으로 발현되어 부친으로부터 유래된 HYMA1 유전자만을 보인 일과성 신생아 당뇨병 1례를 경험하였다. 생후 18일된 여아가 거설증과 반복되는 고혈당으로 입원하였다. 거설증과 함께 큰 대천문, 작은 턱, 두드러진 눈을 보였으며 혈중 포도당 농도는 200-300 mg/dL로 유지되다가 입원 2일 후부터 인슐린 투여 없이도 정상 범위로 유지되었다. 모체로부터 유래된 메틸화된 대립유전자 유무를 확인하기 위하여 말초 혈액으로부터 genomic DNA를 추출하여 bisulfite를 처리한 후, 메틸화 특이 중합 효소 연쇄 반응으로 HYMAI 유전자의 일부분을 증폭시키고, 제한 효소 BssHII를 이용한 제한 효소 절편 길이 다형성 (restriction fragment length polymorphism, RFLP) 분석을 이용하여 HYMAI 유전자의 메틸화 여부를 확인한 결과, HYMAI 유전자의 메틸화 결함을 보여 부친에서 유래된 HYMAI 유전자만을 갖고 있음을 확인하였다. HYMAI 유전자의 메틸화 검사를 통해 6번 염색체의 각인된 유전자가 증명되었으며 메틸화 결함으로 인해 일과성 신생아 당뇨병이 발생하였다.

Keywords

Acknowledgement

Supported by : Korean Ministry of Health and Welfare

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