STUDIES ON MCCUNE-ALBRIGHT SYNDROME

麦库恩-奥尔布赖特综合征的研究

基本信息

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

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A SPIEGEL其他文献

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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
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    --
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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 NEPHROGENIC DIABETES INSIDIPUS
肾性尿崩症的研究
  • 批准号:
    3840502
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
STUDIES ON A CALCIUM SENSING RECEPTOR
钙传感受体的研究
  • 批准号:
    3754521
  • 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:
STUDIES ON NEPHROGENIC DIABETES INSIPIDUS
肾性尿崩症的研究
  • 批准号:
    5202014
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

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