Molecular genetics of Digeorge syndrome and related disorders

迪乔治综合征及相关疾病的分子遗传学

• 批准号: 07670861
• 负责人: KURAHASHI Hiroki
• 金额: $ 1.15万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670861/
• 关键词: DiGeorge syndrome; Contruncal anomaly face; Velo-cardio-facial syndrome; CATCH22; Contiguous gene syndrome; 22q11; Deletion; Repetivive seguence

Patients with several congenital anomaly syndrome, such as DiGeorge syndrome, conotruncal anomaly face syndrome, commonly have a deletion at 22q11. The acronym CATCH22 is now used for such syndromes, for they are thought to consist a contiguous gene syndrome. Although several cDNA have been mapped in this deletion, it is unknown whether they play roles in development of the syndrome. In order to localize the CATCH22 critical region, the refined deletion map of the 100 patients have been constructed using many genomic clones scattered in the deletion. As a result, patients were devided into three types of deletion ; common large deletion, proximal deletion, and distal deletioon. We identified two critical regions in the common deletion, which will provide important information for identification of the disease-causing gene. The phenotype-genotype correlation showed that CATCH22 is not a contiguous gene syndrome. Most patients have the common large deletion, suggesting that there lies characteristic repetitive sequences which easily cause the deletion. We also localized the the boundary of the common large deletion, which would be a help for analysis of the deletion breakpoint.

患有几种先天性异常综合征的患者，如DiGeorge综合征、圆锥动脉干异常面部综合征，通常在22 q11处存在缺失。CATCH 22的首字母缩写现在被用于这些综合征，因为它们被认为是由一个连续的基因综合征。虽然几个cDNA已被定位在这个缺失，这是未知的，他们是否发挥作用，在发展中的综合征。为了定位CATCH 22关键区域，使用分散在缺失中的许多基因组克隆构建了100名患者的精细缺失图谱。结果，患者被分为三种类型的缺失：常见的大缺失，近端缺失和远端缺失。我们确定了共同缺失中的两个关键区域，这将为致病基因的鉴定提供重要信息。表型-基因型相关性表明CATCH 22不是一个相邻基因综合征。大多数患者存在常见的大缺失，提示存在易引起缺失的特征性重复序列。我们还定位了常见的大缺失的边界，这将有助于分析缺失断点。

项目成果

Hiroki Kurahashi: "Another critical region for 22q11 deletion in CATCH22 syndrome : A study of 100 patients." Am J Medical Genetics. (in press).

Hiroki Kurahashi：“CATCH22 综合征中 22q11 缺失的另一个关键区域：一项针对 100 名患者的研究。”

Hiroki Kurahashi: "Deletion mapping of 22q11 in CATCH22 syndrome : Identification of a second critical region" Am J Human Genetics. in press.

Hiroki Kurahashi：“CATCH22 综合征中 22q11 的删除映射：第二个关键区域的识别”Am J Human Genetics。

Yoshio Makita: "Idiopathic hypoparathyroidism in two patients with 22q11 microdeletion." J Medical Genetics. 32. 669 (1996)

Yoshio Makita：“两名 22q11 微缺失患者的特发性甲状旁腺功能减退症。”

Hiroki Kurahashi, Kenzo Akagi, Thomas Melot, Olivier Delattre, Gilles Thomas, Shintaro Okada, Shin-ichiro Tkai and Isamu Nishisho: "Refined mapping of eight cosmid markers on human chromosome 22" Jpn J Human Genetics. 39. 243-248 (1994)

Hiroki Kurahashi、Kenzo Akagi、Thomas Melot、Olivier Delattre、Gilles Thomas、Shintaro Okada、Shin-ichiro Tkai 和 Isamu Nishisho：“人类 22 号染色体上八个粘粒标记的精细定位”Jpn J Human Genetics。

Hiroki Kurahashi: "Isolation and mapping of cosmid markers on human chromosome 22,including one within the submicroscopically deleted region of DiGeorge syndrome." Human Genetics. 93. 248-254 (1994)

Hiroki Kurahashi：“人类 22 号染色体上粘粒标记的分离和定位，其中包括迪乔治综合征亚显微缺失区域内的一个。”