Clinical genetics of Kallmann syndrome
Clinical genetics of Kallmann syndrome
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DOI：
10.1016/j.ando.2010.02.005
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发表时间：
2010-05-01
影响因子：
3.1
通讯作者：
Hardelin, J. -P.
中科院分区：
文献类型：
--
作者：
Dode, C.;Hardelin, J. -P.
卡尔曼综合征（KS）合并低促性腺激素性性腺功能减退（HH）和嗅觉丧失。这是一种临床和遗传异质性疾病。KAL 1编码细胞外糖蛋白anosmin-1，是X染色体连锁隐性形式的疾病（KAL 1）的原因。分别编码成纤维细胞生长因子受体-1和成纤维细胞生长因子-8的FGFR 1或FGF 8的突变是常染色体显性形式的不完全遗传（KAL 2）的基础。编码前动力蛋白受体-2和前动力蛋白-2的PROK 2和PROK 2突变已在杂合、纯合和复合杂合状态中发现。这两个基因可能参与常染色体隐性单基因（KAL 3）和双基因/寡基因KS传播模式。在不到30%的KS患者中发现了上述任何一种KS基因的突变，这表明与疾病有关的其他基因仍有待发现。值得注意的是，KS也可能是包括CHARGE综合征在内的多效性发育疾病的一部分;这种疾病在大多数情况下由编码染色体结构域解旋酶DNA结合蛋白的CHD 7中的新突变引起。(C)2010年Elsevier Masson SAS。All rights reserved.
The Kallmann syndrome (KS) combines hypogonadotropic hypogonadism (HH) with anosmia. This is a clinically and genetically heterogeneous disease. KAL1, encoding the extracellular glycoprotein anosmin-1, is responsible for the X chromosome-linked recessive form of the disease (KAL1). Mutations in FGFR1 or FGF8, encoding fibroblast growth factor receptor-1 and fibroblast growth factor-8, respectively, underlie an autosomal dominant form with incomplete penetrance (KAL2). Mutations in PROKR2 and PROK2, encoding prokineticin receptor-2 and prokineticin-2, have been found in heterozygous, homozygous, and compound heterozygous states. These two genes are likely to be involved both in autosomal recessive monogenic (KAL3) and digenic/oligogenic KS transmission modes. Mutations in any of the above-mentioned KS genes have been found in less than 30% of the KS patients, which indicates that other genes involved in the disease remain to be discovered. Notably, KS may also be part of pleiotropic developmental diseases including CHARGE syndrome; this disease results in most cases from neomutations in CHD7 that encodes a chromodomain helicase DNA-binding protein. (C) 2010 Elsevier Masson SAS. All rights reserved.