The etiology and molecular genetics of human pigmentation disorders.
The etiology and molecular genetics of human pigmentation disorders.
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DOI：
10.1002/wdev.72
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发表时间：
2013-05
影响因子：
--
通讯作者：
Pavan, William J.
中科院分区：
文献类型：
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作者：
Baxter, Laura L.;Pavan, William J.
色素沉着被定义为色素在皮肤、头发和眼睛中的着色，它是独特的，因为色素沉着的位置、数量和类型提供了调节色素生成细胞、黑素细胞途径中遗传异质性的视觉表现。人类这种遗传异质性的范围从正常色素沉着表型到病理性色素沉着表型。临床上正常的人类色素沉着包括各种皮肤和头发颜色以及点状色素沉着，例如黑素细胞痣（痣）或雀斑（雀斑），而临床上异常的人类色素沉着表现出色素水平显着减少或增加，分别称为色素沉着不足和色素沉着过度。对色素沉着背后的分子遗传学的阐明揭示了对黑素细胞发育和功能重要的基因。此外，许多色素沉着疾病在黑素细胞以外的细胞中显示出额外的缺陷，并且对这些疾病中的遗传损伤的鉴定揭示了多效性基因，其中单个基因通常在不同的细胞类型中需要多种功能。因此，揭开易于观察的色素沉着疾病的遗传学，已经确定了黑素细胞和不太明显的细胞类型/组织之间的分子相似性，揭示了共同的细胞起源和/或共同的遗传调控途径。在此，我们讨论值得注意的人类色素沉着疾病及其相关的遗传改变，重点关注色素沉着异常的发育遗传学对于理解控制黑素细胞发育和功能的正常途径具有指导意义的事实。
Pigmentation, defined as the placement of pigment in skin, hair, and eyes for coloration, is distinctive because the location, amount, and type of pigmentation provides a visual manifestation of genetic heterogeneity in pathways regulating the pigment-producing cells, melanocytes. The scope of this genetic heterogeneity in humans ranges from normal to pathological pigmentation phenotypes. Clinically normal human pigmentation encompasses a variety of skin and hair color as well as with punctate pigmentation such as melanocytic nevi (moles) or ephelides (freckles), while clinically abnormal human pigmentation exhibits markedly reduced or increased pigment levels, known as hypopigmentation and hyperpigmentation, respectively. Elucidation of the molecular genetics underlying pigmentation has revealed genes important for melanocyte development and function. Furthermore, many pigmentation disorders show additional defects in cells other than melanocytes, and identification of the genetic insults in these disorders has revealed pleiotropic genes, where a single gene is required for various functions, often in different cell types. Thus unravelling the genetics of easily visualized pigmentation disorders has identified molecular similarities between melanocytes and less visible cell types/tissues, revealing a common cellular origin and/or common genetic regulatory pathways. Herein we discuss notable human pigmentation disorders and their associated genetic alterations, focusing on the fact that the developmental genetics of pigmentation abnormalities is instructive for understanding normal pathways governing development and function of melanocytes.