STUDIES ON MCCUNE-ALBRIGHT SYNDROME
麦库恩-奥尔布赖特综合征的研究
基本信息
- 批准号:3754550
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
McCune-Albright syndrome (MAS) is an non-genetic disorder in which
affected subjects show a variety of seemingly unrelated abnormalities
including polyostotic fibrous dysplasia, pigmented skin lesions (cafe-au-
lait spots), and autonomous hyperfunction of various endocrine organs
including gonads, anterior pituitary, thyroid, and adrenal cortex. The
endocrine abnormalities lead to precocious puberty, gigantism/acromegaly,
hyperthyroidism, and hypercortisolism. The cause of this sporadic
disorder has been enigmatic, but speculations have centered on a defect
in signal transduction leading to endocrine hyperfunction. The
distribution of skin lesions has also suggested the possibility of a
somatic mutation acquired early in embryogenesis and affecting only a
subset of cells (mosaicism). Since a G protein mutation could plausibly
explain the endocrine manifestations, we searched for and found mutations
of the Gs-alpha gene that lead to constitutive activation of the Gs
protein. These mutations were found in a mosaic distribution; notably,
mutant gene was undetectable in normal-appearing portions of endocrine
glands, but as present at heterozygous levels in neoplastic portions of
endocrine tissue. Mutant Gs-alpha was also detected in dysplastic bone
lesions, both in the polyostotic, "classical" form of MAS and in a "form
fruste" of the disease, monostotic fibrous dysplasia. Occurrence of
mutant Gs-alpha in organs such as heart and liver suggest a possible role
in "non-classical" manifestations, including sudden death. Our studies
suggest that MAS is caused by a somatic mutation in the Gs-alpha gene
occurring early in development and found in a mosaic distribution. More
focal manifestations of the disease such as monostotic fibrous dysplasia
may be caused by somatic mutation of the Gs-alpha gene occurring later
in development.
McCune-Albright综合征(MAS)是一种非遗传性疾病,
受影响的受试者表现出各种看似无关的异常
包括多骨纤维性发育不良、色素性皮肤病变(P-AU-1)、
乳斑),以及各种内分泌器官的自主性功能亢进
包括性腺、垂体前叶、甲状腺和肾上腺皮质。 的
内分泌异常导致性早熟、发育迟缓/肢端肥大症,
甲状腺机能亢进和皮质醇增多症 这种零星的原因
混乱一直是个谜,但猜测集中在缺陷上
导致内分泌功能亢进 的
皮肤病变的分布也表明了
体细胞突变在胚胎发生早期获得,只影响一个
细胞亚群(镶嵌现象)。 因为G蛋白突变可能
解释内分泌的表现,我们寻找并发现了
导致Gs-α基因的组成性激活,
蛋白 这些突变被发现呈镶嵌分布;值得注意的是,
突变基因在内分泌正常的部分是检测不到的,
腺体,但作为目前在杂合水平的肿瘤部分,
内分泌组织 在发育不良的骨中也检测到突变型GS-α
病变,包括多发性、“经典”形式的MAS和“典型”形式的MAS
“fruste”的疾病,单骨纤维发育不良。 发生
心脏和肝脏等器官中的突变型Gs-alpha表明,
在“非经典”的表现,包括猝死。 我们的研究
表明MAS是由Gs-alpha基因的体细胞突变引起的
在发育的早期出现,呈镶嵌分布。 更
疾病的局灶性表现,如单骨纤维异常增殖症
可能是由Gs-alpha基因的体细胞突变引起的,
参与发展.
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('A SPIEGEL', 18)}}的其他基金
STUDIES ON PSEUDOHYPOPARATHYROIDISM AND RELATED DISORDERS
假性甲状旁腺功能减退症及相关疾病的研究
- 批准号:
3840499 - 财政年份:
- 资助金额:
-- - 项目类别:
GUANINE NUCLEOTIDE BINDING PROTEINS AS RECEPTOR-EFFECTOR COUPLERS
作为受体-效应器偶联剂的鸟嘌呤核苷酸结合蛋白
- 批准号:
3776957 - 财政年份:
- 资助金额:
-- - 项目类别:
GUANINE NUCLEOTIDE BINDING PROTEINS AS RECEPTOR-EFFECTOR COUPLERS
作为受体-效应器偶联剂的鸟嘌呤核苷酸结合蛋白
- 批准号:
3754548 - 财政年份:
- 资助金额:
-- - 项目类别:
GUANINE NUCLEOTIDE BINDING PROTEINS AS RECEPTOR-EFFECTOR COUPLERS
作为受体-效应器偶联剂的鸟嘌呤核苷酸结合蛋白
- 批准号:
5202010 - 财政年份:
- 资助金额:
-- - 项目类别:
MOLECULAR BIOLOGIC STUDIES ON THE CAUSE OF PARATHYROID NEOPLASIA
甲状旁腺肿瘤病因的分子生物学研究
- 批准号:
3918280 - 财政年份:
- 资助金额:
-- - 项目类别:
MOLECULAR BIOLOGIC STUDIES ON THE CAUSE OF PARATHYROID NEOPLASIA
甲状旁腺肿瘤病因的分子生物学研究
- 批准号:
3855431 - 财政年份:
- 资助金额:
-- - 项目类别:
STUDIES ON PSEUDOHYPOPARATHYROIDISM AND RELATED DISORDERS
假性甲状旁腺功能减退症及相关疾病的研究
- 批准号:
3918282 - 财政年份:
- 资助金额:
-- - 项目类别:
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