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.

对几种原因不明的先天性异常综合征进行了遗传学研究，无论其是否由遗传决定。（1）对8例Arscog综合征、7例Beckwith-Wiedemann综合征（BWS）、3例de Lange综合征、12例Prader-Willi综合征（PWS）和1例歌舞伎化妆（KMS）患者进行了高分辨染色体显带研究。所有PWS患者均在15 q11 -12区域缺失，1例KMS患者存在inv（Y）。（2）对5个BWS家系和文献报道的19个BWS家系进行了分离研究。结果表明，分离率为0.51 ~ 0.066，性别比为1，无男传家系，有4个家系存在三代传。我们的结论是这种疾病是以常染色体显性遗传方式传播的。(3)A进一步改进了鉴定人类近端着丝粒染色体异型性的方法，其特征在于高分辨显带和双重Q-R显带相结合。（4）对4例婴儿型甘油激酶缺乏症患者进行了高分辨显带分析，均显示Xp 21区域缺失。使用Xp 21区域内的几个克隆DNA作为探针进行Southern杂交分析。结果表明，不同患者的DNA缺失长度不同，但5例患者共有的缺失片段仅限于pERT 87 -15位点和C7位点之间的片段。（5）以克隆的p3-21和#34为探针，对6例BWS患者进行Southern杂交分析。所有患者都有一个拷贝的这样的序列，而正常对照组有两个拷贝，这表明用这些探针进行分析使产前诊断疾病成为可能。

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。