A Study on the Etiology of Congenital Anomaly Syndromes of Unknown Cause: Cytogenetic Study with High-Resolution Banding and Origin of Abnormal Chromosomes.

不明原因先天性异常综合征的病因学研究：高分辨率显带的细胞遗传学研究和异常染色体的起源。

• 批准号: 60480468
• 负责人: NIIKAWA Norio
• 金额: $ 1.28万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480468/
• 关键词: Chromosome abnormality; Origin of chromosome abnormality; Micro-deletion of chromosome; Gene deletion; Prader-Willi syndrome; 乳児型グリセロールキナーゼ欠損症

Several congenital anomaly syndromes of unknown cause were studied genetically whether they are genetically determined. The results of the study are as follows: (1)Eight Arscog syndrome patients, 7 Beckwith-Wiedemann syndrome (BWS) patients, 3 de Lange syndrome patients, 12 Prader-Willi syndrome (PWS) patients, and one Kabuki make-up patients (KMS) were studied with high-resolution chromosome bandings. All PWS patients showed a deletion in 15q11-12 region, and one KMS patients have inv(Y). (2)Segregation study was performed on our 5 BWS families and on 19 such families from the literature. Results showed the segregation rate of 0.51 0.066, sex ratio of 1, absence of the family showing male-to-male transmission, and presense of 4 families where the disease was transmitted through 3 generations. We concluded that the disease is transmitted in an autosomal dominant mode of inheritance. (3)A further improved method for identifying heteromorphisms of human acrocentric chromosomes was developed, which is characterized by a combination of high-resolution banding and a dual Q-R banding. (4)High-resolution banding analysis was performed on 4 patients with infantile glycerol kinase deficiency, showing a deletion around the Xp21 region in all. Southern hybridization analyses were performed using several cloned DNAs within the Xp21 region as probes. The results indicate that DNA deletions were different in length with different patients, but the deleted segment common to the five patients was confined to a segment between the locus of pERT87-15 and that of C7. (5)Southern analyses were performed on 6 BWS patients with cloned DNAs p3-21 and #34 as probes. All patients have one copy of such sequences compared with 2 copies in normal controls, suggesting that analyses with these probes make a prenatal diagnosis of the diesease possible.

从遗传上确定了几种未知原因的先天性异常综合征。该研究的结果如下：（1）八名ARSCOG综合征患者，7名Beckwith-Wiedemann综合征（BWS）患者，3名DE Lange综合征患者，12名Prader-Willi综合征（PWS）患者和1名Kabuki化妆患者（KMS）用高分辨率的染色体带进行了研究。所有PWS患者在15q11-12区域均显示缺失，一名KMS患者患有INV（Y）。 （2）对我们的5个BWS家庭和文献中的19个家庭进行了隔离研究。结果表明，隔离率为0.51 0.066，性别比为1，缺乏家庭向男性传播的家庭以及4个疾病传播到3代疾病的家族的预言。我们得出的结论是，该疾病以常染色体显性遗传模式传播。 （3）开发了一种进一步改进的方法，用于鉴定人类杂质染色体的异态性，其特征是高分辨率谱带和双Q-R频带的结合。 （4）对4例婴儿甘油激酶缺乏症患者进行了高分辨率带分析，总共显示了XP21区域周围的缺失。使用XP21区域内的几个克隆DNA作为探针进行了南部杂交分析。结果表明，DNA缺失的长度不同，不同患者的长度不同，但是五名患者共有的已删除片段仅限于PERT87-15和C7的基因座之间的细分市场。 （5）对6个克隆DNAS P3-21和＃34作为探针的6例BWS患者进行了南部分析。与正常对照中的2个副本相比，所有患者均具有此类序列的一份副本，这表明使用这些探针进行分析使得对抑郁症的产前诊断成为可能。

项目成果

Yoshihiro,Jinno;: "Restriction fragment length polymorphisms in the 5'end region of the human argininosuccinate synthetase gene." Journal of inherited metabolic diseases.9. 317-320 (1986)

Yoshihiro，Jinno；：“人精氨琥珀酸合成酶基因 5 端区域的限制性片段长度多态性。”

松本正: 医学のあゆみ. 139. 349-350 (1986)

松本正：医学史。139. 349-350 (1986)

Norio,Niikawa;: "The Wiedemann-Beckwith syndrome; Pedigree studies on five families with evidence for autosomal dominant inheritance with variable expressivity." American Journal of Medical Genetics. 24. 41-55 (1986)

Norio,Niikawa；：“Wiedemann-Beckwith 综合征；对五个家族的系谱研究，有证据表明具有可变表达性的常染色体显性遗传。”

Yoshihiro, Jinno;: "Localization of the human prealbumin gene to 18p11.1-q12.3 by gene dose effect study of Southern blot hybridization." Japanese Journal of Human Genetics. 31. 243-248 (1986)

Yoshihiro, Jinno；：“通过 Southern blot 杂交的基因剂量效应研究将人类前白蛋白基因定位到 18p11.1-q12.3。”

NIIKAWA,Norio: American Journal Medical Genetics. 24. 41-55 (1986)

NIIKAWA，Norio：美国医学遗传学杂志。