소아에서 당뇨병의 특징과 임상증상

양세원,Yang, Se-Won 사단법인 한국당뇨협회 2005 당뇨 Vol.184 No.-

한국인 안드로젠 저항성 증후군 환자의 안드로젠 수용체 유전자 변이 양상

박서영(Seo Yeong Park),최영민(Young Min Choi),박성효(Sung Hyo Park),양세원(Se Won Yang),구승엽(Seung Yup Ku),김석현(Seok Hyun Kim),김수응(Soo Woong Kim),백제승(Jai Seung Paik),양도훈(Do Hoon Yang),최두석(Doo Seok Choi),권혁찬(Hyuck C 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.4

N/A Androgen insensitivity syndrome (AIS) is a X-linked disorder of sexual differentiation resulting from defective androgen receptor (AR) function. Androgens are secreted by the testes of 46,XY individuals, but there is loss of target organ response to the hormone. The abnormalities of AR are due to defects in the AR gene, and many mutations causing AIS have been reported since the cloning of AR gene. In this study, we analyzed the AR genes in twelve Korean patients with androgen insensitivity syndrome: 9 patients with complete AIS and 3 patients with partial AIS. DNAs were isolated from patients with AIS, and the coding region of AR gene was amplified by a polymerase chain reaction using 7 pairs of primers (exon B-H). Sequence analysis of the AR gene was performed using direct sequencing and single strand conformational polymorphism (SSCP). The AR gene mutations were identified in 7 out of 12 patients: 6 of 9 patients with complete AIS, and one of 3 patients with partial AIS. Mutations found were as follows: the point mutation (ATT→ACT) at position 680 of exon D, point mutation (TGG→TGC) at position 751 of exon E, point mutation (CAA→TAA) at position 792 of exon F, point mutations (CGC→TGC, GTG→ATG) at position 855 and 866 of exon G, and the deletion of 13 nucleotides (CGTATCATTGCAT) at position 840 of exon G, respectively. To the best of our knowledge, the point mutations found in exon D, exon E, and exon F, and the deletion in exon G have not been observed before. SSCP revealed bands with abnormal mobility in 10 out of 12 patients tested. Mutations were found 5 out of these 10 patients. The other two patients showed no abnormal band on SSCP, but showed mutations by direct sequencing. In conclusion, we have demonstrated the AR gene mutations, including three novel mutations, in Korean patients with AIS, and these abnormalities might be related to the pathogenesis of androgen insensitivity syndrome.

한국인 정신지체 환자에 있어서 취약 X증후군의 빈도 : 세포유전학적 및 분자유전학적 분석

최영민(Young Min Choi),황도영(Do Yeong Hwang),전종관(Jong Kwan Jun),최진(Jin Choe),박성효(Sung Hyo Park),노미경(Mee Kyung Noh),오선경(Sun Kyung Oh),구승엽(Seung Yup Ku),서창석(Chang Suk Suh),김석현(Seok Hyun Kim),양세원(Se Won Yang) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.11

취약 X증후군은 정신지체를 일으키는 가장 흔한 유전성 질환으로서 외국의 경우 정신지체 환자의 0.2-2.7%를 차지하는 것으로 알려져 있으며 이는 분자유전학적 방법에 의한 정확한 진단에 근거하고 있다. 그러나 국내 정신지체 환자들에서 취약 X증후군의 정확한 유병율이 밝혀져 있지 못하다. 이에 본 연구에서는 분자유전학적 검사 방법을 이용하여 한국인 정신지체 환자에 있어서 취약 X증후군의 빈도를 파악하고자 하였다. 한국인 정신지체 환자 212명 및 가계 구성원들을 대상으로 취약 X증후군 진단을 위한 세포유전학적 검사와 분자유전학적 검사를 시행하였다. 분자유전학적 검사로서는 남자 환자들의 경우 일차적으로 중합효소연쇄반응을 시행하였으며, 결과가 불분명한 경우 Southern blot 분석을 수행하였다. 여자 환자들의 경우 Southern blot 분석을 수행하였다. 세포유전학 검사상 정신지체환자 212명중 6명(2.8%)에서 취약 X염색체가 관찰되었다. 분자유적학적 검사에서도 정신지체환자 212명중 6명(2.8%)이 취약 X 증후군으로 판명되었으며, 이들은 모두 세포유전학 검사에서 취약 X염색체가 보인 환자였으며 모두 남성들이었다. 취약 X증후군으로 판명된 6명의 환자들의 모친 6명, 즉 보인자들에서 분자유전학적 검사를 시행한 결과 보인자 양상을 나타내었다. 그러나 이들에서 세포유전학적 검사를 시행하였으며 이들중 1명(16/7%)에서만이 취약 X염색체가 관찰되었다. 그리고 취약 X증후군으로 판정된 환자의 부친 2명과 남동생 1명에서 분자유전학적 검사를 시행한 결과 정상으로 판정되었다. 112명의 정신지체 환자들을 대상으로 Klentaq1과 Pfu polymerase를 사용하는 새로운 PCR 방법과 기존의 Exo(-) Pfu polymerase를 이용한 방법을 비교한 결과 동일한 결과를 얻었으며, Klentaq1과 Pfu polymerase를 사용하는 실험 기법상 편리하다는 점에서 추천된다고 하겠다. 이상의 결과 한국인 정신지체 환자에 있어서 취약 X증후군의 유병율은 2.8%였으며, Caucasian에서의 유병율과 유의한 차이가 없었다. 그리고 진단 결과에 있어서 세포유전학적 방법과 분자유전학적 방법은 일치하였다. Fragile X syndrome is the most common cause of inherited mental retardation. It accounts for 0.2% - 2.7% of patients with mental retardation, based upon the molecular genetic diagnosis. However, the exact prevalence of fragile X syndrome in Korean patients with mental retardation is unknown. We have performed cytogenetic and molecular analysis for fragile X syndrome in 212 Korean patients with mental retardation. Among them, six patients (2.8%) was identified as carrying fragile X syndrome by both cytogenetic and molecular analysis. The results by cytogenetic analysis was identical to those by molecular analysis. Cytogenetic analysis of 6 carriers (mothers of patients with proven fragile X syndrome) showed a fragile X chromosome in one patients (16.7%) while molecular analysis revealed premutation in all patients. PCR method using Klentaq1과 Pfu polymerase showed the same results as those by PCR method using Exo(-) Pfu polymerase, but the former method is recommended because of its simplicity in technical aspect. These data suggest that the prevalence of fragile X syndrome in Korean patients with mental retardation is 2.8%, not significantly different from those in Caucasians.

최근 성장장애에서 성장호르몬 치료

양세원 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.6

골연령 측정에서 Greulich-Pyle 법과 Tanner-Whitehouse 법의 비교 분석

양세원,김세영 대한내분비학회 1998 Endocrinology and metabolism Vol.13 No.2

Backgrounnd: Bone age measurements have clinical significance in estimation of growth status and prediction of final adult height. Mostly used methods of bone age measurements are Tanner Whitehouse method(TW2) and Greulich-Pyle method(OP). TW2 is known to be more accurate method in determining the bone age, compared to GP. But GP is being used more widely despite some shortcomings, because TW2 is time consuming and need special training. In this study, we observed the correlation between GP and TW2 to evaluate which bone age among three portions of hand and wrist[metacarpals and phalanges(GP1), carpal bones(GP2), distai radius and ulna (GP3)], measured by GP, was more correlated with the bone age, measured by TW2. Methods: Left hand/wrist radiographs were taken from 100 prepubertal children with normal growth. These radiogrphs were reviewed by two pediatric endocrinologists independently. Bone ages using TW2 were measured at first, and then GP1, GP2, and GP3 were measured. These bone ages had been compared with TW2, using SAS computer program. Results: The mean chronological age of 100 children was 10.0+-2.5 years(5 years to 14.7 years range, 63 males and 37 females). The bone age by TW2 was 9.0+- 2.6 years(2.3 to 13.6 years). The bone age by GP1, GP2, and GP3 were 8.8+-2.5 years, 8.7+-2.9 years, and 8.3+-2.8 years, respectively. Bone ages by TW2 were significantly closer to the chronological age than those by GP. The Pea~rson correlation coefficients of GP1, GP2, and GP3 in eomparison to TW2 were 0,87(p=0.0001), 0.94(p=0.0001), and 0.91(p=0.0001), respectively, There are significant correlatkm between bone ages by TW2 and GP. Bone ages by GP2 and GP3 were statistically significantly different from those by TW2(P$lt;0.01). Bone ages by GP1 has no statistical difference with that by TW2(P=0.64). Conelusion: TW2 method is more accurate than GP method in determining the bone age, but it needs time-consuming and laborious efforts. We suggest that the use of GP method for the metacarpals and phalanges can result in a considerable saving of time with no significant loss of accuracy and reproducibility (J Kor Soc Endocrinol 13:198-204, 1998).

성장호르몬 결핍증 환아에서 국내의 유전자재조합기술로 합성된 성장호르몬(DA-3002)의 성장효과

이병철,양세원,김덕희,유한욱,고철우,정우영 대한내분비학회 1998 Endocrinology and metabolism Vol.13 No.4

Background : Recently authentic human growth hormone(hGH) has produced in the E coli K-12, W3110 by recombinant DNA tecbnology in Korea In this paper, the clinical efficacy and immunogenicity of this GH was shdied in 38 children with growth hormone deficiency during therapy of 1 year. Methods: The subjects of this study were aged 4.9-13.9 years, diagnosed by failure of plasma GH to respond to insulin-induced hypoglycemia, arginine and/or L-dopa loading and height below -2 standard deviation of mean for their chronological age. Each patient received GH 0.5-0.7IU/kg/week subcutaneously in 6-7 divided doses. During treatment, vital signs, height, body weight and bone age were checked every 3 months. Complete blood count, urinalysis, blood chemistry and thyroid hormone were checked before and every 6 months. The measurement of serum IGF-1 level and antibody against hGH were performed before and every 6 months during therapy of I year. Result: The height velocities significantly increased from 3.3 +- 1.5cm/year to 10.1 +- 2.5 and 9.0 +- 1.8cm/year at 6 and 12 months of therapy, respectively. The height standard deviation score for chronological age were significantly improved from -2.141.50 to -1.74 +- 1.43 and -1.54 +- 1.38 at 6 and 12 months of therapy with increasing ratio of bone age to chronological age from 0.72 +- 0.15 at pretreatment to 0.76 +- 0.15 at 6 month, 0.79 +- 0.16 at 12 month of therapy. The plasma IGF-1 level significantly increased during treatment. One of 36 patients(2.8%) showed positive antibody against hGH after 1 year of treatment. During therapy of 1 year, unwanted and remarkable clinical side effect were not observed in all subjects. Conclusion: These results indicate that this E. coli derived authentic recombinant growth hormone is very effective in stimulating linear growth in children with growth hormone deficiency. (J kor Soc Endocrinol 13: 526-535, 1998)

인슐린의존성 당뇨병의 표지자로서 항GAD 항체

김목현,박용수,고경수,양세원,이성희,김태화,홍경만,양현종,정준용 대한당뇨병학회 1996 Diabetes and Metabolism Journal Vol.20 No.2

소아에서 발생한 인슐린의존성당뇨병의 임상적 특성

조보연,이홍규,신찬수,고광욱,오태근,고창순,김성연,박경수,양세원 대한당뇨병학회 1994 Diabetes and Metabolism Journal Vol.18 No.4